Fibromyalgia also due to advancing paternal age?
Pharmacogenomics. 2007 Jan;8(1):67-74. Links
The genetics of fibromyalgia syndrome.Buskila D, Sarzi-Puttini P, Ablin JN.
1Ben Gurion University, Department of Medicine H, Soroka Medical Center and Faculty of Health Sciences, Beer Sheva, Israel. dbuskila@bgumail.bgu.ac.il , 2L Sacco University Hospital, Senior Rheumatologist, Rheumatology Unit,Via GB Grassi 74, 20157 Milano, Italy. sarzi@tiscali.it , 3Tel-Aviv University, Departments of Rheumatology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv, Israel. ajacob@post.tau.ac.il.
Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. Although the etiology of FMS is not completely understood, varieties of neuroendocrine disturbances, as well as abnormalities of autonomic function, have been implicated in its pathogenesis. The exposure of a genetically predisposed individual to a host of environmental stressors is presumed to lead to the development of FMS. Fibromyalgia overlaps with several related syndromes, collectively compromising the spectrum of the functional somatic disorder. FMS is characterized by a strong familial aggregation. Recent evidence suggests a role for polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems in the etiopathogenesis of FMS. These polymorphisms are not specific for FMS and are similarly associated with additional comorbid conditions. The mode of inheritance in FMS is unknown, but it is most probably polygenic. Recognition of these gene polymorphisms may help to better subgroup FMS patients and to guide a more rational pharmacological approach. Future genetic studies conducted in larger cohorts of FMS patients and matched control groups may further illuminate the role of genetics in FMS.
PMID: 17187510 [PubMed - as supplied by publisher]
Updated 7/01/06)
Yunus MB, Khan MA, Rawlings KK, Green JR, Olson JM, Shah S.
Genetic linkage analysis of multicase families with fibromyalgia syndrome.
J Rheumatol 1999 Feb;26(2):408-12
"OBJECTIVE: Based on the reports of familial aggregation of fibromyalgia (FM) syndrome, we investigated its possible genetic linkage to HLA by studying multicase families. METHODS: Forty Caucasian multicase families with a diagnosis of FM (American College of Rheumatology criteria) in 2 or more first degree relatives were investigated. Eighty-five affected and 21 unaffected members of 41 sibships were studied. Depression symptomology was assessed by Zung Self-rating Depression Scale (SDS). HLA typing was performed for A, B, and DRB 1 alleles, and haplotypes were determined with no knowledge of the subject's diagnosis. We investigated genetic linkage to the HLA region by evaluating sibships in multicase families. RESULTS: Sibship analysis showed significant genetic linkage of FM to the HLA region (p = 0.028). Subgroup analysis was also performed for 17 families where the proband was also noted to have depression (with an SDS index value > or =60). We found that the presence of depression did not influence the observed results (p = 0.22). CONCLUSION:. Our study of 40 multicase families confirms existence of a possible gene for FM that is linked with the HLA region. Our results should be regarded as preliminary and their independent confirmation by other studies is warranted." [Abstract]
OMIM - Online Mendelian Inheritance in Man: MAJOR HISTOCOMPATIBILITY COMPLEX, CLASS I, A; HLA-A
Horven S, Stiles TC, Holst A, Moen T.
HLA antigens in primary fibromyalgia syndrome.
J Rheumatol 1992 Aug;19(8):1269-70
"HLA antigens, both class I (A,B,C) and II (DR), were determined in 60 patients with primary fibromyalgia syndrome and compared to 159 healthy controls. No significant association between primary fibromyalgia syndrome and alleles of the HLA system was detected." [Abstract]
Burda CD, Cox FR, Osborne P.
Histocompatability antigens in the fibrositis (fibromyalgia) syndrome.
Clin Exp Rheumatol 1986 Oct-Dec;4(4):355-8
"HLA antigen Class I (A, B, C) and II (DR) were determined in a small group of fibrositis (fibromyalgia) patients and normal controls. Sixty-seven percent of fibrositis patients had DR4 versus 30% of normal controls. There was also an increased relative risk (4.5). No statitical significance of other Class I and II antigens in fibrositis was found." [Abstract]
Biasi G, Fioravanti A, Galeazzi M, Marcolongo R.
[Absence of correlation between HLA antigens and fibromyalgia syndrome in Italian patients]
Ann Ital Med Int 1994 Oct-Dec;9(4):228-30
"Fibromyalgia syndrome (FS) is a frequently seen extra-articular rheumatism of unknown etiology. Some authors have suggested a direct role of the immune system in the pathogenesis of the disease while others have found an increased prevalence of some HLA DR and B antigens. The aim of our study was to verify the possible association between HLA and FS in Italian patients with no clinical or immunological evidence of chronic rheumatic inflammatory diseases. Ninety-two consecutive Italian patients were evaluated: 86 were typed for HLA A-B-C antigens and 74 for HLA DR antigens. The study was performed by standard NIH microlymphocytotoxicity technique and by NIH prolonged technique on B lymphocyte purified preparations. There was no statistically significant difference between any HLA A-B-C and DR antigens in the patients compared with the controls. We conclude that in the pathogenesis of FS there is no clear cut evidence of immunologic or genetic involvement." [Abstract]
Gursoy S, Erdal E, Herken H, Madenci E, Alasehirli B, Erdal N.
Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome.
Rheumatol Int 2003 May;23(3):104-7
"Fibromyalgia syndrome (FS) is associated with a neuroendocrinal disorder characterized by abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis, including hyperactive adrenocorticotropic hormone (ACTH) release and adrenal hyporesponsiveness. Catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines and catecholamine-containing drugs. Polymorphism in the gene encodes for the COMT enzyme. For this study, the significance of COMT polymorphism was assessed in FS. There were three polymorphisms of the COMT gene: LL, LH, and HH. The analysis of COMT polymorphism was performed using polymerase chain reaction (PCR). Sixty-one patients with FS and 61 healthy volunteers were included in the study. Although no significant difference was found between LL and LH separately, the LL and LH genotypes together were more highly represented in patients than controls ( P=0.024). In addition, HH genotypes in patients were significantly lower than in the control groups ( P=0.04). There was no significant difference between COMT polymorphism and psychiatric status of the patients as assessed by several psychiatric tests ( P>0.05). In conclusion, COMT polymorphism is of potential pharmacological importance regarding individual differences in the metabolism of catechol drugs and may also be involved in the pathogenesis and treatment of FS through adrenergic mechanisms as well as genetic predisposition to FS." [Abstract]
Gursoy S.
Absence of association of the serotonin transporter gene polymorphism with the mentally healthy subset of fibromyalgia patients.
Clin Rheumatol 2002 Jun;21(3):194-7
"The serotonin transporter (5-HTT) gene is considered to be a promising candidate for genetic involvement in some mood disorders owing to its role in the regulation of serotoninergic neurotransmission. In this study, we aimed to assess the significance of the 5-HTT gene in fibromyalgia syndrome (FS) as well as to find out whether the 5-HTT gene polymorphism is associated with this disease. Fifty-three mentally healthy fibromyalgia patients and 60 unrelated healthy volunteer controls were included in the study. Symptom Checklist-90-Revised (SCL-90-R), Beck Depression Inventory (BDI), and State and Trait Anxiety Inventory tests (STAI-I and II) were applied to both patients and controls. A PCR analysis of 5-HTT gene polymorphism was performed, and the results of the patients with FS and healthy controls were compared. In both FS patients and healthy controls the S/S, S/L and L/L alleles of the 5-HTTLPR genotype were represented in 24.5 % and 33%, 56.6% and 38.3%, and 18.9% and 28.3%, respectively. Additionally, in FS patients and healthy controls the 10/10, 10/12 and 12/12 alleles of the VNTR variant were represented in 5.9% and 11.7, 51% and 36.7%, and 43.1% and 51.7%, respectively. The 5-HTTLPR and VNTR results of the patients and controls were not significantly different ( P>0.05). We concluded that neither 5-HTT nor its polymorphism is associated with FS. Our results also address the frequencies of 5-HTT gene alleles in our population. Further studies are required to better understand the genetic basis of FS." [Abstract]
Offenbaecher M, Bondy B, de Jonge S, Glatzeder K, Kruger M, Schoeps P, Ackenheil M.
Possible association of fibromyalgia with a polymorphism in the serotonin transporter gene regulatory region.
Arthritis Rheum 1999 Nov;42(11):2482-8
"OBJECTIVE: To analyze the genotypes of the promoter region of the serotonin transporter gene (5-HTT) in patients with fibromyalgia (FM). METHODS: Genomic DNA from 62 patients meeting the American College of Rheumatology 1990 criteria for FM and 110 healthy controls was analyzed by polymerase chain reaction. Additionally, the psychopathologic state of 52 of the FM patients was evaluated using the Beck Depression Inventory (BDI) and the Symptom Checklist-90-Revised (SCL-90-R). RESULTS: The 5-HTTLPR genotypes in FM patients versus controls were distributed as follows: L/L 27% versus 34%, L/S 42% versus 50%, and S/S 31% versus 16%. FM patients with the S/S genotype had higher mean scores on the BDI and the SCL-90-R compared with those in the L/L and L/S groups. CONCLUSION: A higher frequency of the S/S genotype of 5-HTT was found in FM patients compared with healthy controls. The S/S subgroup exhibited higher mean levels of depression and psychological distress. These results support the notion of altered serotonin metabolism in at least a subgroup of patients with FM." [Abstract]
Gursoy S, Erdal E, Herken H, Madenci E, Alasehirli B.
Association of T102C polymorphism of the 5-HT2A receptor gene with psychiatric status in fibromyalgia syndrome.
Rheumatol Int 2001 Oct;21(2):58-61
"Serotonin (5-HT) is a key neurotransmitter in the central nervous system. It is suggested that serotonergic dysfunction may be involved in the pathophysiology of fibromyalgia syndrome (FS). In this study, we aimed to investigate T102C polymorphism of the 5-HT2A receptor gene in FS. Fifty-eight patients with FS and 58 unrelated healthy volunteer controls were included in the study. In both groups, the C/C, C/T, and T/T genotypes of the 5-HT gene were represented in 31% (22.4% in controls), 50% (53.4%), and 19% (24.1%), respectively. The 5-HT2A receptor gene polymorphism results were not significantly different between patients and controls (chi squared test, P>0.05). There was a significant correlation between patients with the T/T genotype and the subgroup according to the SCL-90-R test, (analysis of variance, P<0.05). We also saw that patients with the T/T genotype had the lowest pain threshold. CONCLUSION. T102C polymorphism of the 5-HT2A receptor gene is not associated with the etiology of FS. Our results also indicate that the T/T genotype may be responsible for psychiatric symptoms of FS." [Abstract]
Bondy B, Spaeth M, Offenbaecher M, Glatzeder K, Stratz T, Schwarz M, de Jonge S, Kruger M, Engel RR, Farber L, Pongratz DE, Ackenheil M.
The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia.
Neurobiol Dis 1999 Oct;6(5):433-9
"Based on a possible involvement of serotonergic dysfunction in the pathophysiology of fibromyalgia (FM) and on preliminary reports of a possible genetically driven vulnerability for this disorder we investigated the silent T102C polymorphism of the 5-HT2A-receptor gene in 168 FM patients and 115 healthy controls. Our results showed a significantly different genotype distribution in FM patients with a decrease in T/T and an increase in both T/C and C/C genotypes as compared to the control population (Fisher's Exact test, two-sided, P = 0.008). However, the increase in allele-C102 frequency felt short of significance (P = 0.07). Correlation of genotypes to clinical parameters revealed no influences on age of onset, duration of disease or psychopathological symptoms, measured with the Beck Depression Inventory and the symptom checklist SCL-90-R. In contrast to that the pain score, being a self reported information on pain severity, was significantly higher in patients of the T/T genotype (Mann-Whitney U test, P = 0.028). This suggests that the T102-allele might be involved in the complex circuits of nociception. However, the T102C polymorphism is not directly involved in the aetiology of FM but might be in linkage dysequilibrium with the true functional variant, which has to be unravelled." [Abstract]
Frank B, Niesler B, Bondy B, Späth M, Pongratz DE, Ackenheil M, Fischer C, Rappold G
Mutational analysis of serotonin receptor genes: HTR3A and HTR3B in fibromyalgia patients.
Clin Rheumatol. 2004 Aug;23(4):338-44.
The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in numerous human disorders. Dysfunction of serotonergic neurotransmission is thought to play a major role in the pathophysiology of the fibromyalgia syndrome (FMS) which is characterised by non-restorative sleep and severe pain. In our study, both serotonin receptor subunit genes, HTR3A and HTR3B, have been investigated for sequence variations in FMS patients in order to reveal a possible involvement in the aetiology of FMS. We examined DNA samples from 48 patients with FMS representing sporadic cases by single-strand conformation polymorphism (SSCP) and denaturing high-performance liquid chromatography (dHPLC) analysis, sequenced samples with conspicuous patterns and performed statistical calculations. HTR3A mutational analysis revealed one novel as well as five known sequence variations. Investigating HTR3B, we detected seven formerly described mutations and one novel sequence variant. Statistical computation rated all variants as probably non-disease-related polymorphisms. Nevertheless, one might speculate about an effect of the respective sequence variants on the severity of the disease. Sequence variants of the serotonin receptor subunit genes HTR3A and HTR3B indicate no obvious significance in the aetiology of fibromyalgia, yet they represent the basis for future studies on their pharmacogenetic relevance. [Abstract]
Su SY, Chen JJ, Lai CC, Chen CM, Tsai FJ
The association between fibromyalgia and polymorphism of monoamine oxidase A and interleukin-4.
Clin Rheumatol. 2006 Mar 18;
Because fibromyalgia (FM) is often comorbid with anxiety, and monoamine oxidase A (MAOA) was reported to be associated with anxiety, we determine if there is MAOA gene polymorphism associated with FM patients. Moreover, interleukin 4 (IL-4) was found to be an important cytokine participating in the immunologic pathway of T-helper 2 (Th-2) cells, in this study, we search if the genetic polymorphism of IL-4 intron3 could be demonstrated in FM patients. The genotype of sixty-two FM patients was compared with that of control subjects. The polymorphism of IL-4 intron3 variable number of tandem repeats (VNTR) was demonstrated by performing the genomic polymerase chain reaction (PCR) and analyzing the length of PCR product. Furthermore, the MAOA 941 G to T polymorphism was also determined by PCR-RFLP (restriction fragment length polymorphism) analysis. The MAOA 941 position genotype polymorphism between FM and control subjects was found neither statistically different in male (p=0.60) or female (p=0.52), nor total allelic frequency (p=0.52). Similarly, the difference of IL-4 intron3 polymorphism between FM and control was neither existing in genotype (p=0.06), nor allele frequency (p=0.07). The result suggests either the genetic linkage between FM and anxiety or that between FM and immunologic diseases are weak. Accordingly, the MAOA 941 position and IL-4 intron3 polymorphisms are not susceptible markers to predict FM. [Abstract]
Blanco LE, de Serres FJ, Ferna?dez-Bustillo E, Kassam DA, Arbesú D, Rodríguez C, Torre JC
alpha1-Antitrypsin and fibromyalgia: new data in favour of the inflammatory hypothesis of fibromyalgia.
Med Hypotheses. 2005;64(4):759-69.
alpha1-Antitrypsin (AAT) circulates in high serum concentrations, and impregnates most body tissues. AAT has a broad anti-inflammatory spectrum, and modulates most inflammatory reactions occurring in human body. Recently, a possible relationship between AAT deficiency (AAT-D) and fibromyalgia (FM) has been raised, with the finding that intravenous infusions of purified human AAT efficiently controlled FM symptoms in two patients with severe hereditary AAT-D. On the other hand, functional magnetic resonance imaging has detected a significant greater activity in pain sensitive areas of the brain in patients with FM, in response to cutaneous stimuli, providing further evidence for a physiological explanation for FM pain. In recent studies abnormal profiles of inflammation markers in serum and biopsies have been found in FM patients. Since most of these inflammation mediators can be inhibited by AAT, these observations would suggest that at least a subset of the FM syndrome could be related to an inflammatory process, possibly due to an imbalance between inflammatory and anti-inflammatory substances, in the soft body tissues. Future directions of research would be: (1) to develop epidemiological studies to determine the gene frequency of AAT deficiency alleles in FM patients; (2) implementation of a double-blind placebo-controlled clinical trial to determine the specific role of AAT augmentation therapy in AAT-D patients with FM; (3) identification of specific laboratory markers for diagnostic and clinical evaluation purposes in FM; (4) application of the newest medical imaging techniques for diagnosis; and (5) identification of genetic, familial, and environmental risk factors suspected to participate in the FM syndrome development. [Abstract]
Buskila D, Neumann L
Genetics of fibromyalgia.
Curr Pain Headache Rep. 2005 Oct;9(5):313-5.
The pathogenesis of fibromyalgia (FM) and related conditions is not entirely understood. Recent evidence suggests that these syndromes may share heritable pathophysiologic features. Familial studies suggest that genetic and familial factors may play a role in the etiopathogenesis of these conditions. There is evidence that polymorphisms of genes in the serotoninergic and catecholaminergic systems are linked to the pathophysiology of FM and related conditions and are associated with personality traits. The precise role of genetic factors in the etiopathology of FM remains unknown, but it is likely that several genes are operating together to initiate this syndrome. Larger longitudinal studies are needed to better clarify the role of genetics in the development of FM. [Abstract]
Buskila D, Neumann L.
Fibromyalgia syndrome (FM) and nonarticular tenderness in relatives of patients with FM.
J Rheumatol 1997 May;24(5):941-4
"OBJECTIVE: To determine the prevalence of fibromyalgia (FM) and to assess nonarticular tenderness in relatives of patients with FM. METHODS: Thirty female patients with FM randomly chosen from 117 of their close relatives (parents, brothers, sisters, children, husbands) were assessed for nonarticular tenderness. A count of 18 tender points was conducted by thumb palpation, and tenderness thresholds were assessed by dolorimetry at 9 tender sites. FM was diagnosed according to the 1990 American College of Rheumatology criteria. RESULTS: The prevalence of FM among blood relatives of patients with FM was 26%, and among their husbands 19%. FM prevalence in male relatives was 14%, and in female relatives 41%. The mean tender point counts of male and female young relatives was significantly higher than that of controls: 6.1 vs 0.2 (p < 0.01), and 4.4 vs 0.4 (p < 0.01) respectively. Similarly, adult relatives had considerably higher mean tender point counts than controls: 4.0 vs 0.04 (p < 0.01) and 10.3 vs 0.28 (p < 0.01) respectively, for males and females. CONCLUSION: Relatives of patients with FM have a higher prevalence of FM and are more tender than the general population, as recently reported and shown in a healthy control group. This finding can be attributed to genetic and environmental factors." [Abstract]
Buskila D, Neumann L, Hazanov I, Carmi R.
Familial aggregation in the fibromyalgia syndrome.
Semin Arthritis Rheum 1996 Dec;26(3):605-11
"The authors studied the familial occurrence of fibromyalgia (FMS) to determine a possible role of genetic and familial factors in this syndrome. Fifty-eight offspring aged 5 to 46 years (35 males and 23 females) from 20 complete nuclear families ascertained through affected mothers with FMS were clinically evaluated for FMS according to the ACR 1990 diagnostic criteria. FMS symptoms, quality of life, physical functioning, and dolorimetry thresholds were assessed in all subjects. Sixteen offspring (28%) were found to have FMS. The M/F ratio among the affected was 0.8 compared with 1.5 in the whole study group. Offspring with and without FMS did not differ on anxiety, depression, global well-being, quality of life, and physical functioning. A high prevalence of FMS was observed among offspring of FMS mothers. Because psychological and familial factors were not different in children with and without FMS, the high familial occurrence of this syndrome may be attributable to genetic factors." [Abstract]
Pellegrino MJ, Waylonis GW, Sommer A.
Familial occurrence of primary fibromyalgia.
Arch Phys Med Rehabil 1989 Jan;70(1):61-3
"Seventeen families of patients with primary fibromyalgia were studied for evidence of inherited primary fibromyalgia. Fifty parents and siblings were included in the analysis. Twenty-six (52%, mean age 33.5 years) had characteristic symptoms and findings of primary fibromyalgia. Eleven (22%, mean age 28 years) were asymptomatic but had clinical evidence of abnormal muscle consistency to palpation without tender or trigger points. One person had clinical evidence of lupus. Thirteen (26%) had no evidence of fibromyalgia or abnormal muscle consistency. The mode of inheritance was autosomal dominant. Identical twins are described who developed symptoms of primary fibromyalgia within six months of each other, as are two brothers who developed abnormal palpable muscle consistency years before acquiring the characteristic findings of the fibromyalgia syndrome. Primary fibromyalgia may be an inherited condition with a variable latent stage before clinical expression of the disease." [Abstract]
Hudson JI, Goldenberg DL, Pope HG Jr, Keck PE Jr, Schlesinger L.
Comorbidity of fibromyalgia with medical and psychiatric disorders.
Am J Med 1992 Apr;92(4):363-7
"PURPOSE: Patients with fibromyalgia have been reported to display high rates of several concomitant medical and psychiatric disorders, including migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder. To test further these and other possible associations, we assessed the personal and family histories of a broad range of medical and psychiatric disorders in patients with fibromyalgia. PATIENTS AND METHODS: Subjects were 33 women (mean age 42.1 years) who each met American College of Rheumatology criteria for fibromyalgia and presented to a rheumatologist at a tertiary referral center. They received the Structured Clinical Interview for DSM-III-R (SCID); a supplemental interview, in SCID format, for other medical and psychiatric disorders, including migraine, irritable bowel syndrome, and chronic fatigue syndrome; and an interview for family history of medical and psychiatric disorders. RESULTS: Patients with fibromyalgia displayed high lifetime rates of migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder. They also exhibited high rates of familial major mood disorder. CONCLUSIONS: The finding that migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder are frequently comorbid with fibromyalgia is consistent with the hypothesis that these various disorders may share a common physiologic abnormality." [Abstract]
Offenbaecher M, Glatzeder K, Ackenheil M.
Self-reported depression, familial history of depression and fibromyalgia (FM), and psychological distress in patients with FM.
Z Rheumatol 1998;57 Suppl 2:94-6
"The prevalence of FM in the general population is estimated at 2%. FM is among the three most common diagnoses in ambulatory adult rheumatology practice. To study the degree of depression, the familial history of depression and FM, as well as the psychological distress in our FM population, we mailed a standardized questionnaire to 304 FM patients. The response rate was 33%. We found BDI scores higher than 21 in 27% of the patients indicating clinical relevant depression. The patients had high levels of global distress measured with the SCL-90-R as well as elevated scores in the subscales. Twenty three percent had a familial history of depression, 46% a familial history of FM, and 46% had been diagnosed with depression in the past." [Abstract]
Aaron LA, Herrell R, Ashton S, Belcourt M, Schmaling K, Goldberg J, Buchwald D.
Comorbid clinical conditions in chronic fatigue: a co-twin control study.
J Gen Intern Med 2001 Jan;16(1):24-31
"OBJECTIVES: Chronically fatiguing illness, defined as fatigue for at least 6 months, has been associated with various physical health conditions. Our objective was to determine whether there is a significant relationship between chronically fatiguing illness and 10 clinical conditions that frequently appear to be associated with fatigue, adjusting for the potentially confounding effects of psychiatric illness. DESIGN: A co-twin control study controlling for genetic and many environmental factors by comparing chronically fatigued twins with their nonfatigued co-twins. SETTING: A nationally distributed volunteer twin registry. PARTICIPANTS: The study included 127 twin pairs in which one member of the pair experienced fatigue of at least 6 months' duration and the co-twin was healthy and denied chronic fatigue. Fatigued twins were classified into 3 levels using increasingly stringent diagnostic criteria. MEASUREMENTS AND MAIN RESULTS: Twins reported on a history of fibromyalgia, irritable bowel syndrome, multiple chemical sensitivities, temporomandibular disorder, interstitial cystitis, postconcussion syndrome, tension headache, chronic low back pain, chronic pelvic pain (women), and chronic nonbacterial prostatitis (men). The prevalence of these comorbid clinical conditions was significantly higher in the fatigued twins compared to their nonfatigued co-twins. Most notably, compared to their nonfatigued co-twins, the chronically fatigued twins had higher rates of fibromyalgia (> 70% vs < 10%) and irritable bowel syndrome (> 50% vs < 5%). The strongest associations were observed between chronic fatigue and fibromyalgia (odds ratios > 20), irritable bowel syndrome, chronic pelvic pain, multiple chemical sensitivities, and temporomandibular disorder (all with odds ratios > or = 4). Regression analysis suggested that the number of comorbid clinical conditions associated with chronic fatigue could not be attributed solely to psychiatric illness. CONCLUSIONS: Chronically fatiguing illnesses were associated with high rates of many other clinical conditions. Thus, patients with chronic fatigue may present a complex clinical picture that poses diagnostic and management challenges. Nonetheless, clinicians should assess such patients for the presence of comorbid clinical conditions. Future research should provide a better understanding of the temporal relationship of the onset of fatigue and these conditions, and develop strategies for early intervention." [Abstract]
Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P.
High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis.
Hum Reprod 2002 Oct;17(10):2715-24
"BACKGROUND: Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue and atopic disorders is higher in women with endometriosis than in the general female population. METHODS AND RESULTS: A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members with surgically diagnosed endometriosis. Almost all responders had pain (99%), and many reported infertility (41%). Compared with published rates in the general USA female population, women with endometriosis had higher rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001), rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus (0.8 versus 0.04%, P < 0.0001), Sjogren's syndrome (0.6 versus 0.03%, P < 0.0001) and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001 respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001 respectively). CONCLUSIONS: Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma are all significantly more common in women with endometriosis than in women in the general USA population." [Abstract]
Berg AM, Naides SJ, Simms RW.
Established fibromyalgia syndrome and parvovirus B19 infection.
J Rheumatol 1993 Nov;20(11):1941-3
"OBJECTIVE. To determine the seroprevalence of prior and persistent parvovirus B19 (B19) infection in a group of patients with fibromyalgia (FS) compared with controls. METHODS. Fifteen female patients with FS who recalled a viral prodrome (+VP) preceding the onset of FS symptoms and eleven patients with FS who did not recall any such illness (-VP) were selected from a referral practice. We excluded patients with FS who described a history of trauma prior to the onset of FS symptoms. Twenty-six female medical workers served as controls. Serum IgM and IgG anti-B19 antibodies were measured by ELISA. Polymerase chain reaction (PCR) products from serum were analyzed by dot blot hybridization for B19 DNA. Fisher's 2-tailed exact test was used to compare the proportion of positive serologies in each group. RESULTS. No patient or control had positive IgM levels. For all patients with FS, the prevalence of prior B19 infection was comparable to that of healthy controls (11/26 vs 12/26, p = 1.00) and that of the general population. No significant difference was found in the prevalence of prior B19 infection in FS + VP and FS-VP patients (8/15 vs 3/11, p = 0.25). None of the patients or controls showed evidence for persistent B19 viremia, as determined by PCR analysis. CONCLUSION. Our data do not suggest that B19 plays a pathogenic role in this population of patients with FS. Testing for IgM against B19 within 2-3 months of symptom onset may prove more helpful in further defining the role of B19 in FS." [Abstract]
Kato K, Sullivan PF, Evengård B, Pedersen NL
Importance of genetic influences on chronic widespread pain.
Arthritis Rheum. 2006 May;54(5):1682-6.
OBJECTIVE: To estimate the relative importance of genetic and environmental factors in chronic widespread pain, and to assess whether there are sex differences in the type or magnitude of these influences. METHODS: Data were collected from a national sample of twins > or = 42 years of age, all of whom were participants in the Swedish Twin Registry. The presence of chronic widespread pain was assessed via computer-assisted telephone interviews, which were conducted between 1998 and 2002, using the American College of Rheumatology criteria for fibromyalgia. No clinical examinations were performed. In preliminary analyses, probandwise concordance rates and tetrachoric correlations were calculated. Structural equation modeling was then performed to estimate additive genetic, shared environmental, and nonshared environmental sources of variability in susceptibility for the development of chronic widespread pain. RESULTS: Of 61,355 eligible twins, 44,897 individuals (73.2%) responded to the interview. Both members of 15,950 pairs responded to the items regarding pain symptoms; of these pairs, 4,170 were monozygotic, 5,881 were same-sex dizygotic, and 5,755 were opposite-sex dizygotic. The prevalence of chronic widespread pain was 4.1%, and the ratio of women to men was 3.3 to 1. Probandwise concordance rates and tetrachoric correlations suggested modest genetic influences for both women and men. Genetic and shared environmental influences explained approximately half of the total variance, with no indication of sex differences in either the type or magnitude of these influences. CONCLUSION: Individual differences in the likelihood of developing chronic widespread pain reflect modest genetic influences. There are no significant sex differences in the type or expression of the genes responsible for chronic widespread pain or in the magnitude of the relative importance of these influences on chronic widespread pain. [Abstract]
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Su SY, Chen JJ, Lai CC, Chen CM, Tsai FJ
The association between fibromyalgia and polymorphism of monoamine oxidase A and interleukin-4.
Clin Rheumatol. 2007 Jan;26(1):12-6.
Because fibromyalgia (FM) is often comorbid with anxiety, and monoamine oxidase A (MAOA) was reported to be associated with anxiety, we determine if there is MAOA gene polymorphism associated with FM patients. Moreover, interleukin 4 (IL-4) was found to be an important cytokine participating in the immunologic pathway of T-helper 2 (Th-2) cells, in this study, we search if the genetic polymorphism of IL-4 intron3 could be demonstrated in FM patients. The genotype of sixty-two FM patients was compared with that of control subjects. The polymorphism of IL-4 intron3 variable number of tandem repeats (VNTR) was demonstrated by performing the genomic polymerase chain reaction (PCR) and analyzing the length of PCR product. Furthermore, the MAOA 941 G to T polymorphism was also determined by PCR-RFLP (restriction fragment length polymorphism) analysis. The MAOA 941 position genotype polymorphism between FM and control subjects was found neither statistically different in male (p=0.60) or female (p=0.52), nor total allelic frequency (p=0.52). Similarly, the difference of IL-4 intron3 polymorphism between FM and control was neither existing in genotype (p=0.06), nor allele frequency (p=0.07). The result suggests either the genetic linkage between FM and anxiety or that between FM and immunologic diseases are weak. Accordingly, the MAOA 941 position and IL-4 intron3 polymorphisms are not susceptible markers to predict FM. [Abstract]
Buskila D, Sarzi-Puttini P, Ablin JN
The genetics of fibromyalgia syndrome.
Pharmacogenomics. 2007 Jan;8(1):67-74.
Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. Although the etiology of FMS is not completely understood, varieties of neuroendocrine disturbances, as well as abnormalities of autonomic function, have been implicated in its pathogenesis. The exposure of a genetically predisposed individual to a host of environmental stressors is presumed to lead to the development of FMS. Fibromyalgia overlaps with several related syndromes, collectively compromising the spectrum of the functional somatic disorder. FMS is characterized by a strong familial aggregation. Recent evidence suggests a role for polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems in the etiopathogenesis of FMS. These polymorphisms are not specific for FMS and are similarly associated with additional comorbid conditions. The mode of inheritance in FMS is unknown, but it is most probably polygenic. Recognition of these gene polymorphisms may help to better subgroup FMS patients and to guide a more rational pharmacological approach. Future genetic studies conducted in larger cohorts of FMS patients and matched control groups may further illuminate the role of genetics in FMS. [Abstract]
Ala?ehirli B, Demiryürek S, Ar?ca E, Gürsoy S, Demiryürek AT
No evidence for an association between the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene and fibromyalgia syndrome.
Rheumatol Int. 2007 Jan;27(3):275-280.
The objective of this study was to analyze the genotype distributions and allele frequencies for the Glu298Asp (G894T) polymorphism of the eNOS gene and the serum nitric oxide level among the patients with fibromyalgia syndrome (FS). Ninety-six fibromyalgia patients and 79 unrelated healthy volunteer controls were included in the study. All patients and controls were females. Genomic DNA from 96 patients meeting the American College of Rheumatology 1990 criteria for FS and 79 healthy controls was analyzed by polymerase chain reaction. A polymerase chain reaction-restriction fragment-length polymorphism analysis of eNOS gene polymorphism was performed, and the results of the patients with FS and healthy controls were compared. Ozone-based chemiluminescence assay with Sievers NO Analyzer was used to measure the serum nitric oxide levels. Neither the frequencies of the Glu298Asp genotypes nor the serum nitric oxide levels showed a significant difference between the groups. These results suggested that FS of the Turkish population seemed to develop without any alterations in eNOS Glu298Asp genotype frequency and the serum nitric oxide level. [Abstract]
Harris RE, Clauw DJ
How do we know that the pain in fibromyalgia is "real"?
Curr Pain Headache Rep. 2006 Dec;10(6):403-7.
Fibromyalgia is a common idiopathic pain condition often resulting in increased morbidity and disability in patients. The lack of peripheral abnormalities in this disease has led clinicians and researchers alike to question if this syndrome represents a valid entity. Recent genetic findings suggest that specific gene mutations may predispose individuals to develop fibromyalgia. In addition, neurobiological studies indicate that fibromyalgia patients have abnormalities within central brain structures that normally encode pain sensations in healthy pain-free controls. Future studies that focus on central neurobiological and/or genetic influences in fibromyalgia may bring insight into mechanisms of this problematic disease and ultimately result in improved treatments. [Abstract]
Ablin JN, Cohen H, Buskila D
Mechanisms of Disease: genetics of fibromyalgia.
Nat Clin Pract Rheumatol. 2006 Dec;2(12):671-8.
Fibromyalgia is characterized by widespread pain and tenderness, and has a significant familial component. The etiology of fibromyalgia remains unclear, but genetic factors seem to have a significant role, and are influenced by environmental factors. Research over the past two decades has demonstrated that genetic polymorphisms in the serotoninergic, dopaminergic and catecholaminergic systems of pain transmission and processing are involved in the etiology of fibromyalgia, but additional candidates continue to emerge. Fibromyalgia is thought to belong to the group of affective spectrum disorders, which include related psychiatric and medical disorders. As the concept of affective spectrum disorders continues to evolve, progress in the understanding of the genetic basis of related functional disorders, such as irritable bowel syndrome and post-traumatic-stress disorder, is aiding our understanding of the genetic basis of fibromyalgia. [Abstract]
Uçeyler N, Valenza R, Stock M, Schedel R, Sprotte G, Sommer C
Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain.
Arthritis Rheum. 2006 Aug;54(8):2656-64.
OBJECTIVE: The term chronic widespread pain refers to a group of painful diseases of poorly understood pathophysiology. One major subgroup is fibromyalgia (FM), as defined by the criteria of the American College of Rheumatology. Among other hypotheses, a potential pathophysiologic role of cytokines in chronic widespread pain has been proposed. We undertook this study to investigate whether cytokine profiles differ in patients with chronic widespread pain and controls. METHODS: We analyzed cytokine expression patterns in 40 patients with chronic widespread pain (26 of whom had FM), 40 age- and sex-matched healthy controls, and an additional 15 patients with chronic widespread pain who were recruited from a different center. Expression of messenger RNA (mRNA) for interleukin-2 (IL-2), IL-4, IL-8, IL-10, tumor necrosis factor alpha (TNFalpha), and transforming growth factor beta1 (TGFbeta1) in peripheral blood was analyzed using quantitative real-time polymerase chain reaction (PCR). Serum protein levels were measured by enzyme-linked immunosorbent assay. RESULTS: We found significantly lower relative gene expression (P < 0.0001 for IL-4; P = 0.03 for IL-10) and lower levels of serum protein concentrations (P < 0.0001 for IL-4; P = 0.04 for IL-10) of the Th2 cytokines IL-4 and IL-10 in patients with chronic widespread pain than in the control group. This finding was corroborated in an additional group of 15 patients with chronic widespread pain. There were no significant differences between the groups in levels of mRNA for IL-2, IL-8, TNFalpha, or TGFbeta1. Protein data paralleled the real-time PCR results. CONCLUSION: Chronic widespread pain is associated with a lack of antiinflammatory and analgesic Th2 cytokine activity, which may contribute to its pathogenesis. [Abstract]
Dadabhoy D, Clauw DJ
Therapy Insight: fibromyalgia--a different type of pain needing a different type of treatment.
Nat Clin Pract Rheumatol. 2006 Jul;2(7):364-72.
In the past decade, we have made tremendous progress in our understanding of fibromyalgia, which is now recognized as one of many 'central' pain syndromes that are common in the general population. Specific genes that might confer an increased risk of developing fibromyalgia syndrome are beginning to be identified and the environment (in this case exposure to stressors) might also have a significant effect on triggering the expression of symptoms. After developing the syndrome, the hallmark aberration noted in individuals with fibromyalgia is augmented central pain processing. Insights from research suggest that fibromyalgia and related syndromes require a multimodal management program that is different from the standard used to treat peripheral pain (i.e. acute or inflammatory pain). Instead of the nonsteroidal anti-inflammatory drugs and opioids commonly used in the treatment of peripheral pain, the recommended drugs for central pain conditions are neuroactive compounds that downregulate sensory processing. The most efficacious compounds that are currently available include the tricyclic drugs and mixed reuptake inhibitors that simultaneously increase serotonin and norepinephrine concentrations in the central nervous system. Other compounds that increase levels of single monoamines (serotonin, norepinephrine or dopamine), and anticonvulsants also show efficacy in this condition. In addition to these pharmacologic therapies, which are useful in improving symptoms, nonpharmacologic therapies such as exercise and cognitive behavioral therapy are useful treatments for restoring function to an individual with fibromyalgia. [Abstract]
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The genetics of fibromyalgia syndrome.Buskila D, Sarzi-Puttini P, Ablin JN.
1Ben Gurion University, Department of Medicine H, Soroka Medical Center and Faculty of Health Sciences, Beer Sheva, Israel. dbuskila@bgumail.bgu.ac.il , 2L Sacco University Hospital, Senior Rheumatologist, Rheumatology Unit,Via GB Grassi 74, 20157 Milano, Italy. sarzi@tiscali.it , 3Tel-Aviv University, Departments of Rheumatology, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv, Israel. ajacob@post.tau.ac.il.
Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. Although the etiology of FMS is not completely understood, varieties of neuroendocrine disturbances, as well as abnormalities of autonomic function, have been implicated in its pathogenesis. The exposure of a genetically predisposed individual to a host of environmental stressors is presumed to lead to the development of FMS. Fibromyalgia overlaps with several related syndromes, collectively compromising the spectrum of the functional somatic disorder. FMS is characterized by a strong familial aggregation. Recent evidence suggests a role for polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems in the etiopathogenesis of FMS. These polymorphisms are not specific for FMS and are similarly associated with additional comorbid conditions. The mode of inheritance in FMS is unknown, but it is most probably polygenic. Recognition of these gene polymorphisms may help to better subgroup FMS patients and to guide a more rational pharmacological approach. Future genetic studies conducted in larger cohorts of FMS patients and matched control groups may further illuminate the role of genetics in FMS.
PMID: 17187510 [PubMed - as supplied by publisher]
Updated 7/01/06)
Yunus MB, Khan MA, Rawlings KK, Green JR, Olson JM, Shah S.
Genetic linkage analysis of multicase families with fibromyalgia syndrome.
J Rheumatol 1999 Feb;26(2):408-12
"OBJECTIVE: Based on the reports of familial aggregation of fibromyalgia (FM) syndrome, we investigated its possible genetic linkage to HLA by studying multicase families. METHODS: Forty Caucasian multicase families with a diagnosis of FM (American College of Rheumatology criteria) in 2 or more first degree relatives were investigated. Eighty-five affected and 21 unaffected members of 41 sibships were studied. Depression symptomology was assessed by Zung Self-rating Depression Scale (SDS). HLA typing was performed for A, B, and DRB 1 alleles, and haplotypes were determined with no knowledge of the subject's diagnosis. We investigated genetic linkage to the HLA region by evaluating sibships in multicase families. RESULTS: Sibship analysis showed significant genetic linkage of FM to the HLA region (p = 0.028). Subgroup analysis was also performed for 17 families where the proband was also noted to have depression (with an SDS index value > or =60). We found that the presence of depression did not influence the observed results (p = 0.22). CONCLUSION:. Our study of 40 multicase families confirms existence of a possible gene for FM that is linked with the HLA region. Our results should be regarded as preliminary and their independent confirmation by other studies is warranted." [Abstract]
OMIM - Online Mendelian Inheritance in Man: MAJOR HISTOCOMPATIBILITY COMPLEX, CLASS I, A; HLA-A
Horven S, Stiles TC, Holst A, Moen T.
HLA antigens in primary fibromyalgia syndrome.
J Rheumatol 1992 Aug;19(8):1269-70
"HLA antigens, both class I (A,B,C) and II (DR), were determined in 60 patients with primary fibromyalgia syndrome and compared to 159 healthy controls. No significant association between primary fibromyalgia syndrome and alleles of the HLA system was detected." [Abstract]
Burda CD, Cox FR, Osborne P.
Histocompatability antigens in the fibrositis (fibromyalgia) syndrome.
Clin Exp Rheumatol 1986 Oct-Dec;4(4):355-8
"HLA antigen Class I (A, B, C) and II (DR) were determined in a small group of fibrositis (fibromyalgia) patients and normal controls. Sixty-seven percent of fibrositis patients had DR4 versus 30% of normal controls. There was also an increased relative risk (4.5). No statitical significance of other Class I and II antigens in fibrositis was found." [Abstract]
Biasi G, Fioravanti A, Galeazzi M, Marcolongo R.
[Absence of correlation between HLA antigens and fibromyalgia syndrome in Italian patients]
Ann Ital Med Int 1994 Oct-Dec;9(4):228-30
"Fibromyalgia syndrome (FS) is a frequently seen extra-articular rheumatism of unknown etiology. Some authors have suggested a direct role of the immune system in the pathogenesis of the disease while others have found an increased prevalence of some HLA DR and B antigens. The aim of our study was to verify the possible association between HLA and FS in Italian patients with no clinical or immunological evidence of chronic rheumatic inflammatory diseases. Ninety-two consecutive Italian patients were evaluated: 86 were typed for HLA A-B-C antigens and 74 for HLA DR antigens. The study was performed by standard NIH microlymphocytotoxicity technique and by NIH prolonged technique on B lymphocyte purified preparations. There was no statistically significant difference between any HLA A-B-C and DR antigens in the patients compared with the controls. We conclude that in the pathogenesis of FS there is no clear cut evidence of immunologic or genetic involvement." [Abstract]
Gursoy S, Erdal E, Herken H, Madenci E, Alasehirli B, Erdal N.
Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome.
Rheumatol Int 2003 May;23(3):104-7
"Fibromyalgia syndrome (FS) is associated with a neuroendocrinal disorder characterized by abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis, including hyperactive adrenocorticotropic hormone (ACTH) release and adrenal hyporesponsiveness. Catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines and catecholamine-containing drugs. Polymorphism in the gene encodes for the COMT enzyme. For this study, the significance of COMT polymorphism was assessed in FS. There were three polymorphisms of the COMT gene: LL, LH, and HH. The analysis of COMT polymorphism was performed using polymerase chain reaction (PCR). Sixty-one patients with FS and 61 healthy volunteers were included in the study. Although no significant difference was found between LL and LH separately, the LL and LH genotypes together were more highly represented in patients than controls ( P=0.024). In addition, HH genotypes in patients were significantly lower than in the control groups ( P=0.04). There was no significant difference between COMT polymorphism and psychiatric status of the patients as assessed by several psychiatric tests ( P>0.05). In conclusion, COMT polymorphism is of potential pharmacological importance regarding individual differences in the metabolism of catechol drugs and may also be involved in the pathogenesis and treatment of FS through adrenergic mechanisms as well as genetic predisposition to FS." [Abstract]
Gursoy S.
Absence of association of the serotonin transporter gene polymorphism with the mentally healthy subset of fibromyalgia patients.
Clin Rheumatol 2002 Jun;21(3):194-7
"The serotonin transporter (5-HTT) gene is considered to be a promising candidate for genetic involvement in some mood disorders owing to its role in the regulation of serotoninergic neurotransmission. In this study, we aimed to assess the significance of the 5-HTT gene in fibromyalgia syndrome (FS) as well as to find out whether the 5-HTT gene polymorphism is associated with this disease. Fifty-three mentally healthy fibromyalgia patients and 60 unrelated healthy volunteer controls were included in the study. Symptom Checklist-90-Revised (SCL-90-R), Beck Depression Inventory (BDI), and State and Trait Anxiety Inventory tests (STAI-I and II) were applied to both patients and controls. A PCR analysis of 5-HTT gene polymorphism was performed, and the results of the patients with FS and healthy controls were compared. In both FS patients and healthy controls the S/S, S/L and L/L alleles of the 5-HTTLPR genotype were represented in 24.5 % and 33%, 56.6% and 38.3%, and 18.9% and 28.3%, respectively. Additionally, in FS patients and healthy controls the 10/10, 10/12 and 12/12 alleles of the VNTR variant were represented in 5.9% and 11.7, 51% and 36.7%, and 43.1% and 51.7%, respectively. The 5-HTTLPR and VNTR results of the patients and controls were not significantly different ( P>0.05). We concluded that neither 5-HTT nor its polymorphism is associated with FS. Our results also address the frequencies of 5-HTT gene alleles in our population. Further studies are required to better understand the genetic basis of FS." [Abstract]
Offenbaecher M, Bondy B, de Jonge S, Glatzeder K, Kruger M, Schoeps P, Ackenheil M.
Possible association of fibromyalgia with a polymorphism in the serotonin transporter gene regulatory region.
Arthritis Rheum 1999 Nov;42(11):2482-8
"OBJECTIVE: To analyze the genotypes of the promoter region of the serotonin transporter gene (5-HTT) in patients with fibromyalgia (FM). METHODS: Genomic DNA from 62 patients meeting the American College of Rheumatology 1990 criteria for FM and 110 healthy controls was analyzed by polymerase chain reaction. Additionally, the psychopathologic state of 52 of the FM patients was evaluated using the Beck Depression Inventory (BDI) and the Symptom Checklist-90-Revised (SCL-90-R). RESULTS: The 5-HTTLPR genotypes in FM patients versus controls were distributed as follows: L/L 27% versus 34%, L/S 42% versus 50%, and S/S 31% versus 16%. FM patients with the S/S genotype had higher mean scores on the BDI and the SCL-90-R compared with those in the L/L and L/S groups. CONCLUSION: A higher frequency of the S/S genotype of 5-HTT was found in FM patients compared with healthy controls. The S/S subgroup exhibited higher mean levels of depression and psychological distress. These results support the notion of altered serotonin metabolism in at least a subgroup of patients with FM." [Abstract]
Gursoy S, Erdal E, Herken H, Madenci E, Alasehirli B.
Association of T102C polymorphism of the 5-HT2A receptor gene with psychiatric status in fibromyalgia syndrome.
Rheumatol Int 2001 Oct;21(2):58-61
"Serotonin (5-HT) is a key neurotransmitter in the central nervous system. It is suggested that serotonergic dysfunction may be involved in the pathophysiology of fibromyalgia syndrome (FS). In this study, we aimed to investigate T102C polymorphism of the 5-HT2A receptor gene in FS. Fifty-eight patients with FS and 58 unrelated healthy volunteer controls were included in the study. In both groups, the C/C, C/T, and T/T genotypes of the 5-HT gene were represented in 31% (22.4% in controls), 50% (53.4%), and 19% (24.1%), respectively. The 5-HT2A receptor gene polymorphism results were not significantly different between patients and controls (chi squared test, P>0.05). There was a significant correlation between patients with the T/T genotype and the subgroup according to the SCL-90-R test, (analysis of variance, P<0.05). We also saw that patients with the T/T genotype had the lowest pain threshold. CONCLUSION. T102C polymorphism of the 5-HT2A receptor gene is not associated with the etiology of FS. Our results also indicate that the T/T genotype may be responsible for psychiatric symptoms of FS." [Abstract]
Bondy B, Spaeth M, Offenbaecher M, Glatzeder K, Stratz T, Schwarz M, de Jonge S, Kruger M, Engel RR, Farber L, Pongratz DE, Ackenheil M.
The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia.
Neurobiol Dis 1999 Oct;6(5):433-9
"Based on a possible involvement of serotonergic dysfunction in the pathophysiology of fibromyalgia (FM) and on preliminary reports of a possible genetically driven vulnerability for this disorder we investigated the silent T102C polymorphism of the 5-HT2A-receptor gene in 168 FM patients and 115 healthy controls. Our results showed a significantly different genotype distribution in FM patients with a decrease in T/T and an increase in both T/C and C/C genotypes as compared to the control population (Fisher's Exact test, two-sided, P = 0.008). However, the increase in allele-C102 frequency felt short of significance (P = 0.07). Correlation of genotypes to clinical parameters revealed no influences on age of onset, duration of disease or psychopathological symptoms, measured with the Beck Depression Inventory and the symptom checklist SCL-90-R. In contrast to that the pain score, being a self reported information on pain severity, was significantly higher in patients of the T/T genotype (Mann-Whitney U test, P = 0.028). This suggests that the T102-allele might be involved in the complex circuits of nociception. However, the T102C polymorphism is not directly involved in the aetiology of FM but might be in linkage dysequilibrium with the true functional variant, which has to be unravelled." [Abstract]
Frank B, Niesler B, Bondy B, Späth M, Pongratz DE, Ackenheil M, Fischer C, Rappold G
Mutational analysis of serotonin receptor genes: HTR3A and HTR3B in fibromyalgia patients.
Clin Rheumatol. 2004 Aug;23(4):338-44.
The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in numerous human disorders. Dysfunction of serotonergic neurotransmission is thought to play a major role in the pathophysiology of the fibromyalgia syndrome (FMS) which is characterised by non-restorative sleep and severe pain. In our study, both serotonin receptor subunit genes, HTR3A and HTR3B, have been investigated for sequence variations in FMS patients in order to reveal a possible involvement in the aetiology of FMS. We examined DNA samples from 48 patients with FMS representing sporadic cases by single-strand conformation polymorphism (SSCP) and denaturing high-performance liquid chromatography (dHPLC) analysis, sequenced samples with conspicuous patterns and performed statistical calculations. HTR3A mutational analysis revealed one novel as well as five known sequence variations. Investigating HTR3B, we detected seven formerly described mutations and one novel sequence variant. Statistical computation rated all variants as probably non-disease-related polymorphisms. Nevertheless, one might speculate about an effect of the respective sequence variants on the severity of the disease. Sequence variants of the serotonin receptor subunit genes HTR3A and HTR3B indicate no obvious significance in the aetiology of fibromyalgia, yet they represent the basis for future studies on their pharmacogenetic relevance. [Abstract]
Su SY, Chen JJ, Lai CC, Chen CM, Tsai FJ
The association between fibromyalgia and polymorphism of monoamine oxidase A and interleukin-4.
Clin Rheumatol. 2006 Mar 18;
Because fibromyalgia (FM) is often comorbid with anxiety, and monoamine oxidase A (MAOA) was reported to be associated with anxiety, we determine if there is MAOA gene polymorphism associated with FM patients. Moreover, interleukin 4 (IL-4) was found to be an important cytokine participating in the immunologic pathway of T-helper 2 (Th-2) cells, in this study, we search if the genetic polymorphism of IL-4 intron3 could be demonstrated in FM patients. The genotype of sixty-two FM patients was compared with that of control subjects. The polymorphism of IL-4 intron3 variable number of tandem repeats (VNTR) was demonstrated by performing the genomic polymerase chain reaction (PCR) and analyzing the length of PCR product. Furthermore, the MAOA 941 G to T polymorphism was also determined by PCR-RFLP (restriction fragment length polymorphism) analysis. The MAOA 941 position genotype polymorphism between FM and control subjects was found neither statistically different in male (p=0.60) or female (p=0.52), nor total allelic frequency (p=0.52). Similarly, the difference of IL-4 intron3 polymorphism between FM and control was neither existing in genotype (p=0.06), nor allele frequency (p=0.07). The result suggests either the genetic linkage between FM and anxiety or that between FM and immunologic diseases are weak. Accordingly, the MAOA 941 position and IL-4 intron3 polymorphisms are not susceptible markers to predict FM. [Abstract]
Blanco LE, de Serres FJ, Ferna?dez-Bustillo E, Kassam DA, Arbesú D, Rodríguez C, Torre JC
alpha1-Antitrypsin and fibromyalgia: new data in favour of the inflammatory hypothesis of fibromyalgia.
Med Hypotheses. 2005;64(4):759-69.
alpha1-Antitrypsin (AAT) circulates in high serum concentrations, and impregnates most body tissues. AAT has a broad anti-inflammatory spectrum, and modulates most inflammatory reactions occurring in human body. Recently, a possible relationship between AAT deficiency (AAT-D) and fibromyalgia (FM) has been raised, with the finding that intravenous infusions of purified human AAT efficiently controlled FM symptoms in two patients with severe hereditary AAT-D. On the other hand, functional magnetic resonance imaging has detected a significant greater activity in pain sensitive areas of the brain in patients with FM, in response to cutaneous stimuli, providing further evidence for a physiological explanation for FM pain. In recent studies abnormal profiles of inflammation markers in serum and biopsies have been found in FM patients. Since most of these inflammation mediators can be inhibited by AAT, these observations would suggest that at least a subset of the FM syndrome could be related to an inflammatory process, possibly due to an imbalance between inflammatory and anti-inflammatory substances, in the soft body tissues. Future directions of research would be: (1) to develop epidemiological studies to determine the gene frequency of AAT deficiency alleles in FM patients; (2) implementation of a double-blind placebo-controlled clinical trial to determine the specific role of AAT augmentation therapy in AAT-D patients with FM; (3) identification of specific laboratory markers for diagnostic and clinical evaluation purposes in FM; (4) application of the newest medical imaging techniques for diagnosis; and (5) identification of genetic, familial, and environmental risk factors suspected to participate in the FM syndrome development. [Abstract]
Buskila D, Neumann L
Genetics of fibromyalgia.
Curr Pain Headache Rep. 2005 Oct;9(5):313-5.
The pathogenesis of fibromyalgia (FM) and related conditions is not entirely understood. Recent evidence suggests that these syndromes may share heritable pathophysiologic features. Familial studies suggest that genetic and familial factors may play a role in the etiopathogenesis of these conditions. There is evidence that polymorphisms of genes in the serotoninergic and catecholaminergic systems are linked to the pathophysiology of FM and related conditions and are associated with personality traits. The precise role of genetic factors in the etiopathology of FM remains unknown, but it is likely that several genes are operating together to initiate this syndrome. Larger longitudinal studies are needed to better clarify the role of genetics in the development of FM. [Abstract]
Buskila D, Neumann L.
Fibromyalgia syndrome (FM) and nonarticular tenderness in relatives of patients with FM.
J Rheumatol 1997 May;24(5):941-4
"OBJECTIVE: To determine the prevalence of fibromyalgia (FM) and to assess nonarticular tenderness in relatives of patients with FM. METHODS: Thirty female patients with FM randomly chosen from 117 of their close relatives (parents, brothers, sisters, children, husbands) were assessed for nonarticular tenderness. A count of 18 tender points was conducted by thumb palpation, and tenderness thresholds were assessed by dolorimetry at 9 tender sites. FM was diagnosed according to the 1990 American College of Rheumatology criteria. RESULTS: The prevalence of FM among blood relatives of patients with FM was 26%, and among their husbands 19%. FM prevalence in male relatives was 14%, and in female relatives 41%. The mean tender point counts of male and female young relatives was significantly higher than that of controls: 6.1 vs 0.2 (p < 0.01), and 4.4 vs 0.4 (p < 0.01) respectively. Similarly, adult relatives had considerably higher mean tender point counts than controls: 4.0 vs 0.04 (p < 0.01) and 10.3 vs 0.28 (p < 0.01) respectively, for males and females. CONCLUSION: Relatives of patients with FM have a higher prevalence of FM and are more tender than the general population, as recently reported and shown in a healthy control group. This finding can be attributed to genetic and environmental factors." [Abstract]
Buskila D, Neumann L, Hazanov I, Carmi R.
Familial aggregation in the fibromyalgia syndrome.
Semin Arthritis Rheum 1996 Dec;26(3):605-11
"The authors studied the familial occurrence of fibromyalgia (FMS) to determine a possible role of genetic and familial factors in this syndrome. Fifty-eight offspring aged 5 to 46 years (35 males and 23 females) from 20 complete nuclear families ascertained through affected mothers with FMS were clinically evaluated for FMS according to the ACR 1990 diagnostic criteria. FMS symptoms, quality of life, physical functioning, and dolorimetry thresholds were assessed in all subjects. Sixteen offspring (28%) were found to have FMS. The M/F ratio among the affected was 0.8 compared with 1.5 in the whole study group. Offspring with and without FMS did not differ on anxiety, depression, global well-being, quality of life, and physical functioning. A high prevalence of FMS was observed among offspring of FMS mothers. Because psychological and familial factors were not different in children with and without FMS, the high familial occurrence of this syndrome may be attributable to genetic factors." [Abstract]
Pellegrino MJ, Waylonis GW, Sommer A.
Familial occurrence of primary fibromyalgia.
Arch Phys Med Rehabil 1989 Jan;70(1):61-3
"Seventeen families of patients with primary fibromyalgia were studied for evidence of inherited primary fibromyalgia. Fifty parents and siblings were included in the analysis. Twenty-six (52%, mean age 33.5 years) had characteristic symptoms and findings of primary fibromyalgia. Eleven (22%, mean age 28 years) were asymptomatic but had clinical evidence of abnormal muscle consistency to palpation without tender or trigger points. One person had clinical evidence of lupus. Thirteen (26%) had no evidence of fibromyalgia or abnormal muscle consistency. The mode of inheritance was autosomal dominant. Identical twins are described who developed symptoms of primary fibromyalgia within six months of each other, as are two brothers who developed abnormal palpable muscle consistency years before acquiring the characteristic findings of the fibromyalgia syndrome. Primary fibromyalgia may be an inherited condition with a variable latent stage before clinical expression of the disease." [Abstract]
Hudson JI, Goldenberg DL, Pope HG Jr, Keck PE Jr, Schlesinger L.
Comorbidity of fibromyalgia with medical and psychiatric disorders.
Am J Med 1992 Apr;92(4):363-7
"PURPOSE: Patients with fibromyalgia have been reported to display high rates of several concomitant medical and psychiatric disorders, including migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder. To test further these and other possible associations, we assessed the personal and family histories of a broad range of medical and psychiatric disorders in patients with fibromyalgia. PATIENTS AND METHODS: Subjects were 33 women (mean age 42.1 years) who each met American College of Rheumatology criteria for fibromyalgia and presented to a rheumatologist at a tertiary referral center. They received the Structured Clinical Interview for DSM-III-R (SCID); a supplemental interview, in SCID format, for other medical and psychiatric disorders, including migraine, irritable bowel syndrome, and chronic fatigue syndrome; and an interview for family history of medical and psychiatric disorders. RESULTS: Patients with fibromyalgia displayed high lifetime rates of migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder. They also exhibited high rates of familial major mood disorder. CONCLUSIONS: The finding that migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder are frequently comorbid with fibromyalgia is consistent with the hypothesis that these various disorders may share a common physiologic abnormality." [Abstract]
Offenbaecher M, Glatzeder K, Ackenheil M.
Self-reported depression, familial history of depression and fibromyalgia (FM), and psychological distress in patients with FM.
Z Rheumatol 1998;57 Suppl 2:94-6
"The prevalence of FM in the general population is estimated at 2%. FM is among the three most common diagnoses in ambulatory adult rheumatology practice. To study the degree of depression, the familial history of depression and FM, as well as the psychological distress in our FM population, we mailed a standardized questionnaire to 304 FM patients. The response rate was 33%. We found BDI scores higher than 21 in 27% of the patients indicating clinical relevant depression. The patients had high levels of global distress measured with the SCL-90-R as well as elevated scores in the subscales. Twenty three percent had a familial history of depression, 46% a familial history of FM, and 46% had been diagnosed with depression in the past." [Abstract]
Aaron LA, Herrell R, Ashton S, Belcourt M, Schmaling K, Goldberg J, Buchwald D.
Comorbid clinical conditions in chronic fatigue: a co-twin control study.
J Gen Intern Med 2001 Jan;16(1):24-31
"OBJECTIVES: Chronically fatiguing illness, defined as fatigue for at least 6 months, has been associated with various physical health conditions. Our objective was to determine whether there is a significant relationship between chronically fatiguing illness and 10 clinical conditions that frequently appear to be associated with fatigue, adjusting for the potentially confounding effects of psychiatric illness. DESIGN: A co-twin control study controlling for genetic and many environmental factors by comparing chronically fatigued twins with their nonfatigued co-twins. SETTING: A nationally distributed volunteer twin registry. PARTICIPANTS: The study included 127 twin pairs in which one member of the pair experienced fatigue of at least 6 months' duration and the co-twin was healthy and denied chronic fatigue. Fatigued twins were classified into 3 levels using increasingly stringent diagnostic criteria. MEASUREMENTS AND MAIN RESULTS: Twins reported on a history of fibromyalgia, irritable bowel syndrome, multiple chemical sensitivities, temporomandibular disorder, interstitial cystitis, postconcussion syndrome, tension headache, chronic low back pain, chronic pelvic pain (women), and chronic nonbacterial prostatitis (men). The prevalence of these comorbid clinical conditions was significantly higher in the fatigued twins compared to their nonfatigued co-twins. Most notably, compared to their nonfatigued co-twins, the chronically fatigued twins had higher rates of fibromyalgia (> 70% vs < 10%) and irritable bowel syndrome (> 50% vs < 5%). The strongest associations were observed between chronic fatigue and fibromyalgia (odds ratios > 20), irritable bowel syndrome, chronic pelvic pain, multiple chemical sensitivities, and temporomandibular disorder (all with odds ratios > or = 4). Regression analysis suggested that the number of comorbid clinical conditions associated with chronic fatigue could not be attributed solely to psychiatric illness. CONCLUSIONS: Chronically fatiguing illnesses were associated with high rates of many other clinical conditions. Thus, patients with chronic fatigue may present a complex clinical picture that poses diagnostic and management challenges. Nonetheless, clinicians should assess such patients for the presence of comorbid clinical conditions. Future research should provide a better understanding of the temporal relationship of the onset of fatigue and these conditions, and develop strategies for early intervention." [Abstract]
Sinaii N, Cleary SD, Ballweg ML, Nieman LK, Stratton P.
High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis.
Hum Reprod 2002 Oct;17(10):2715-24
"BACKGROUND: Women with endometriosis may also have associated disorders related to autoimmune dysregulation or pain. This study examined whether the prevalence of autoimmune, chronic pain and fatigue and atopic disorders is higher in women with endometriosis than in the general female population. METHODS AND RESULTS: A cross-sectional survey was conducted in 1998 by the Endometriosis Association of 3680 USA members with surgically diagnosed endometriosis. Almost all responders had pain (99%), and many reported infertility (41%). Compared with published rates in the general USA female population, women with endometriosis had higher rates of hypothyroidism (9.6 versus 1.5%, P < 0.0001), fibromyalgia (5.9 versus 3.4%, P < 0.0001), chronic fatigue syndrome (4.6 versus 0.03%, P < 0.0001), rheumatoid arthritis (1.8 versus 1.2%, P = 0.001), systemic lupus erythematosus (0.8 versus 0.04%, P < 0.0001), Sjogren's syndrome (0.6 versus 0.03%, P < 0.0001) and multiple sclerosis (0.5 versus 0.07%, P < 0.0001), but not hyperthyroidism or diabetes. Allergies and asthma were more common among women with endometriosis alone (61%, P < 0.001 and 12%, P < 0.001 respectively) and highest in those with fibromyalgia or chronic fatigue syndrome (88%, P < 0.001 and 25%, P < 0.001 respectively) than in the USA female population (18%, P < 0.001 and 5%, P < 0.001 respectively). CONCLUSIONS: Hypothyroidism, fibromyalgia, chronic fatigue syndrome, autoimmune diseases, allergies and asthma are all significantly more common in women with endometriosis than in women in the general USA population." [Abstract]
Berg AM, Naides SJ, Simms RW.
Established fibromyalgia syndrome and parvovirus B19 infection.
J Rheumatol 1993 Nov;20(11):1941-3
"OBJECTIVE. To determine the seroprevalence of prior and persistent parvovirus B19 (B19) infection in a group of patients with fibromyalgia (FS) compared with controls. METHODS. Fifteen female patients with FS who recalled a viral prodrome (+VP) preceding the onset of FS symptoms and eleven patients with FS who did not recall any such illness (-VP) were selected from a referral practice. We excluded patients with FS who described a history of trauma prior to the onset of FS symptoms. Twenty-six female medical workers served as controls. Serum IgM and IgG anti-B19 antibodies were measured by ELISA. Polymerase chain reaction (PCR) products from serum were analyzed by dot blot hybridization for B19 DNA. Fisher's 2-tailed exact test was used to compare the proportion of positive serologies in each group. RESULTS. No patient or control had positive IgM levels. For all patients with FS, the prevalence of prior B19 infection was comparable to that of healthy controls (11/26 vs 12/26, p = 1.00) and that of the general population. No significant difference was found in the prevalence of prior B19 infection in FS + VP and FS-VP patients (8/15 vs 3/11, p = 0.25). None of the patients or controls showed evidence for persistent B19 viremia, as determined by PCR analysis. CONCLUSION. Our data do not suggest that B19 plays a pathogenic role in this population of patients with FS. Testing for IgM against B19 within 2-3 months of symptom onset may prove more helpful in further defining the role of B19 in FS." [Abstract]
Kato K, Sullivan PF, Evengård B, Pedersen NL
Importance of genetic influences on chronic widespread pain.
Arthritis Rheum. 2006 May;54(5):1682-6.
OBJECTIVE: To estimate the relative importance of genetic and environmental factors in chronic widespread pain, and to assess whether there are sex differences in the type or magnitude of these influences. METHODS: Data were collected from a national sample of twins > or = 42 years of age, all of whom were participants in the Swedish Twin Registry. The presence of chronic widespread pain was assessed via computer-assisted telephone interviews, which were conducted between 1998 and 2002, using the American College of Rheumatology criteria for fibromyalgia. No clinical examinations were performed. In preliminary analyses, probandwise concordance rates and tetrachoric correlations were calculated. Structural equation modeling was then performed to estimate additive genetic, shared environmental, and nonshared environmental sources of variability in susceptibility for the development of chronic widespread pain. RESULTS: Of 61,355 eligible twins, 44,897 individuals (73.2%) responded to the interview. Both members of 15,950 pairs responded to the items regarding pain symptoms; of these pairs, 4,170 were monozygotic, 5,881 were same-sex dizygotic, and 5,755 were opposite-sex dizygotic. The prevalence of chronic widespread pain was 4.1%, and the ratio of women to men was 3.3 to 1. Probandwise concordance rates and tetrachoric correlations suggested modest genetic influences for both women and men. Genetic and shared environmental influences explained approximately half of the total variance, with no indication of sex differences in either the type or magnitude of these influences. CONCLUSION: Individual differences in the likelihood of developing chronic widespread pain reflect modest genetic influences. There are no significant sex differences in the type or expression of the genes responsible for chronic widespread pain or in the magnitude of the relative importance of these influences on chronic widespread pain. [Abstract]
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Su SY, Chen JJ, Lai CC, Chen CM, Tsai FJ
The association between fibromyalgia and polymorphism of monoamine oxidase A and interleukin-4.
Clin Rheumatol. 2007 Jan;26(1):12-6.
Because fibromyalgia (FM) is often comorbid with anxiety, and monoamine oxidase A (MAOA) was reported to be associated with anxiety, we determine if there is MAOA gene polymorphism associated with FM patients. Moreover, interleukin 4 (IL-4) was found to be an important cytokine participating in the immunologic pathway of T-helper 2 (Th-2) cells, in this study, we search if the genetic polymorphism of IL-4 intron3 could be demonstrated in FM patients. The genotype of sixty-two FM patients was compared with that of control subjects. The polymorphism of IL-4 intron3 variable number of tandem repeats (VNTR) was demonstrated by performing the genomic polymerase chain reaction (PCR) and analyzing the length of PCR product. Furthermore, the MAOA 941 G to T polymorphism was also determined by PCR-RFLP (restriction fragment length polymorphism) analysis. The MAOA 941 position genotype polymorphism between FM and control subjects was found neither statistically different in male (p=0.60) or female (p=0.52), nor total allelic frequency (p=0.52). Similarly, the difference of IL-4 intron3 polymorphism between FM and control was neither existing in genotype (p=0.06), nor allele frequency (p=0.07). The result suggests either the genetic linkage between FM and anxiety or that between FM and immunologic diseases are weak. Accordingly, the MAOA 941 position and IL-4 intron3 polymorphisms are not susceptible markers to predict FM. [Abstract]
Buskila D, Sarzi-Puttini P, Ablin JN
The genetics of fibromyalgia syndrome.
Pharmacogenomics. 2007 Jan;8(1):67-74.
Fibromyalgia syndrome (FMS) is a common chronic widespread pain syndrome mainly affecting women. Although the etiology of FMS is not completely understood, varieties of neuroendocrine disturbances, as well as abnormalities of autonomic function, have been implicated in its pathogenesis. The exposure of a genetically predisposed individual to a host of environmental stressors is presumed to lead to the development of FMS. Fibromyalgia overlaps with several related syndromes, collectively compromising the spectrum of the functional somatic disorder. FMS is characterized by a strong familial aggregation. Recent evidence suggests a role for polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems in the etiopathogenesis of FMS. These polymorphisms are not specific for FMS and are similarly associated with additional comorbid conditions. The mode of inheritance in FMS is unknown, but it is most probably polygenic. Recognition of these gene polymorphisms may help to better subgroup FMS patients and to guide a more rational pharmacological approach. Future genetic studies conducted in larger cohorts of FMS patients and matched control groups may further illuminate the role of genetics in FMS. [Abstract]
Ala?ehirli B, Demiryürek S, Ar?ca E, Gürsoy S, Demiryürek AT
No evidence for an association between the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene and fibromyalgia syndrome.
Rheumatol Int. 2007 Jan;27(3):275-280.
The objective of this study was to analyze the genotype distributions and allele frequencies for the Glu298Asp (G894T) polymorphism of the eNOS gene and the serum nitric oxide level among the patients with fibromyalgia syndrome (FS). Ninety-six fibromyalgia patients and 79 unrelated healthy volunteer controls were included in the study. All patients and controls were females. Genomic DNA from 96 patients meeting the American College of Rheumatology 1990 criteria for FS and 79 healthy controls was analyzed by polymerase chain reaction. A polymerase chain reaction-restriction fragment-length polymorphism analysis of eNOS gene polymorphism was performed, and the results of the patients with FS and healthy controls were compared. Ozone-based chemiluminescence assay with Sievers NO Analyzer was used to measure the serum nitric oxide levels. Neither the frequencies of the Glu298Asp genotypes nor the serum nitric oxide levels showed a significant difference between the groups. These results suggested that FS of the Turkish population seemed to develop without any alterations in eNOS Glu298Asp genotype frequency and the serum nitric oxide level. [Abstract]
Harris RE, Clauw DJ
How do we know that the pain in fibromyalgia is "real"?
Curr Pain Headache Rep. 2006 Dec;10(6):403-7.
Fibromyalgia is a common idiopathic pain condition often resulting in increased morbidity and disability in patients. The lack of peripheral abnormalities in this disease has led clinicians and researchers alike to question if this syndrome represents a valid entity. Recent genetic findings suggest that specific gene mutations may predispose individuals to develop fibromyalgia. In addition, neurobiological studies indicate that fibromyalgia patients have abnormalities within central brain structures that normally encode pain sensations in healthy pain-free controls. Future studies that focus on central neurobiological and/or genetic influences in fibromyalgia may bring insight into mechanisms of this problematic disease and ultimately result in improved treatments. [Abstract]
Ablin JN, Cohen H, Buskila D
Mechanisms of Disease: genetics of fibromyalgia.
Nat Clin Pract Rheumatol. 2006 Dec;2(12):671-8.
Fibromyalgia is characterized by widespread pain and tenderness, and has a significant familial component. The etiology of fibromyalgia remains unclear, but genetic factors seem to have a significant role, and are influenced by environmental factors. Research over the past two decades has demonstrated that genetic polymorphisms in the serotoninergic, dopaminergic and catecholaminergic systems of pain transmission and processing are involved in the etiology of fibromyalgia, but additional candidates continue to emerge. Fibromyalgia is thought to belong to the group of affective spectrum disorders, which include related psychiatric and medical disorders. As the concept of affective spectrum disorders continues to evolve, progress in the understanding of the genetic basis of related functional disorders, such as irritable bowel syndrome and post-traumatic-stress disorder, is aiding our understanding of the genetic basis of fibromyalgia. [Abstract]
Uçeyler N, Valenza R, Stock M, Schedel R, Sprotte G, Sommer C
Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain.
Arthritis Rheum. 2006 Aug;54(8):2656-64.
OBJECTIVE: The term chronic widespread pain refers to a group of painful diseases of poorly understood pathophysiology. One major subgroup is fibromyalgia (FM), as defined by the criteria of the American College of Rheumatology. Among other hypotheses, a potential pathophysiologic role of cytokines in chronic widespread pain has been proposed. We undertook this study to investigate whether cytokine profiles differ in patients with chronic widespread pain and controls. METHODS: We analyzed cytokine expression patterns in 40 patients with chronic widespread pain (26 of whom had FM), 40 age- and sex-matched healthy controls, and an additional 15 patients with chronic widespread pain who were recruited from a different center. Expression of messenger RNA (mRNA) for interleukin-2 (IL-2), IL-4, IL-8, IL-10, tumor necrosis factor alpha (TNFalpha), and transforming growth factor beta1 (TGFbeta1) in peripheral blood was analyzed using quantitative real-time polymerase chain reaction (PCR). Serum protein levels were measured by enzyme-linked immunosorbent assay. RESULTS: We found significantly lower relative gene expression (P < 0.0001 for IL-4; P = 0.03 for IL-10) and lower levels of serum protein concentrations (P < 0.0001 for IL-4; P = 0.04 for IL-10) of the Th2 cytokines IL-4 and IL-10 in patients with chronic widespread pain than in the control group. This finding was corroborated in an additional group of 15 patients with chronic widespread pain. There were no significant differences between the groups in levels of mRNA for IL-2, IL-8, TNFalpha, or TGFbeta1. Protein data paralleled the real-time PCR results. CONCLUSION: Chronic widespread pain is associated with a lack of antiinflammatory and analgesic Th2 cytokine activity, which may contribute to its pathogenesis. [Abstract]
Dadabhoy D, Clauw DJ
Therapy Insight: fibromyalgia--a different type of pain needing a different type of treatment.
Nat Clin Pract Rheumatol. 2006 Jul;2(7):364-72.
In the past decade, we have made tremendous progress in our understanding of fibromyalgia, which is now recognized as one of many 'central' pain syndromes that are common in the general population. Specific genes that might confer an increased risk of developing fibromyalgia syndrome are beginning to be identified and the environment (in this case exposure to stressors) might also have a significant effect on triggering the expression of symptoms. After developing the syndrome, the hallmark aberration noted in individuals with fibromyalgia is augmented central pain processing. Insights from research suggest that fibromyalgia and related syndromes require a multimodal management program that is different from the standard used to treat peripheral pain (i.e. acute or inflammatory pain). Instead of the nonsteroidal anti-inflammatory drugs and opioids commonly used in the treatment of peripheral pain, the recommended drugs for central pain conditions are neuroactive compounds that downregulate sensory processing. The most efficacious compounds that are currently available include the tricyclic drugs and mixed reuptake inhibitors that simultaneously increase serotonin and norepinephrine concentrations in the central nervous system. Other compounds that increase levels of single monoamines (serotonin, norepinephrine or dopamine), and anticonvulsants also show efficacy in this condition. In addition to these pharmacologic therapies, which are useful in improving symptoms, nonpharmacologic therapies such as exercise and cognitive behavioral therapy are useful treatments for restoring function to an individual with fibromyalgia. [Abstract]
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Labels: fibromyalgia, genetics
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