fibromyalgia genetics

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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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Recent Fibromyalgia Genetic Research

1) Sommer C, Häuser W, Burgmer M, Engelhardt R, Gerhold K, Petzke F, Schmidt-Wilcke T, Späth M, Tölle T, Uçeyler N, Wang H, Winkelmann A, Thieme K
[Etiology and pathophysiology of fibromyalgia syndrome].
Schmerz. 2012 Jun;26(3):259-67.
[PubMed Citation] [Order full text from Infotrieve]


2) Tammimäki A, Männistö PT
Catechol-O-methyltransferase gene polymorphism and chronic human pain: a systematic review and meta-analysis.
Pharmacogenet Genomics. 2012 Jun 20;
In human studies, low COMT (catechol-O-methyltransferase) activity has been associated with increased sensitivity to acute clinical preoperative or postoperative pain. We explored the association between the COMT genotype and three chronic pain conditions: migrainous headache, fibromyalgia, or chronic widespread pain and chronic musculoskeletal pain. Furthermore, we evaluated whether COMT genotype affects the efficacy of opioids in chronic pain. After a systematic literature review, we carried out meta-analyses on the three chronic pain conditions. The efficacy of opioids was evaluated using a systematic review only. The meta-analyses showed that fibromyalgia or chronic widespread pain is the only type of chronic pain that could be associated with the COMT single nucleotide polymorphism rs4680 (Val158Met). Met158, which results in the low-activity variant of COMT, is the risk allele. In chronic clinical pain, the effect of the COMT polymorphism depends on the pain condition. Low COMT activity is not associated with migrainous headache or chronic musculoskeletal pain conditions, but it may increase the risk for fibromyalgia or chronic widespread pain. Low COMT activity increases opioid receptors and enhances opioid analgesia and adverse effects in some cancer pains. Findings from animal studies that have utilized COMT inhibitors elucidate the mechanism behind these findings. In rodent pain models, COMT inhibitors are pronociceptive, except for neuropathic pain models, where nitecapone was found to be antiallodynic. The complex interplay between enhanced adrenergic and dopaminergic activity in different parts of the nociceptive system probably explains the complicated actions of low COMT activity. [PubMed Citation] [Order full text from Infotrieve]


3) Martínez-Jauand M, Sitges C, Rodríguez V, Picornell A, Ramon M, Buskila D, Montoya P
Pain sensitivity in fibromyalgia is associated with catechol-O-methyltransferase (COMT) gene.
Eur J Pain. 2012 Apr 24;
BACKGROUND: Recent evidence suggests that genetic factors might contribute to individual differences in pain sensitivity, risk for developing clinical pain conditions and efficacy of pain treatments. The purpose of the present study was to investigate the relationship of three common haplotypes of COMT gene affecting the metabolism of catecholamines on pain sensitivity in patients with fibromyalgia (FM). METHODS: One hundred and thirteen FM patients and 65 age-matched healthy volunteers participated in the study. We genotyped four single-nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4818 and rs4680 or Val158Met) and identified haplotypes previously designated as low (LPS), average (APS) and high pain sensitivity (HPS). Thermal, pressure and touch thresholds were also examined using a quantitative sensory testing protocol. RESULTS: The frequency of genetic variations associated with low COMT enzyme activity was significantly higher in FM patients than in healthy volunteers. FM patients were more sensitive to experimental pain than healthy volunteers and, in particular, FM individuals with the met/met genotype (Val158Met SNP) or the HPS-APS haplotypes showing higher sensitivity to thermal and pressure pain stimuli than patients carrying the LPS haplotype or val alleles (Val158Met SNP). No differences due to genotype or haplotypes were found on non-painful touch thresholds. CONCLUSIONS: According with previous research, our findings revealed that haplotypes of the COMT gene and genotypes of the Val158Met polymorphism play a key role on pain sensitivity in FM patients. [PubMed Citation] [Order full text from Infotrieve]


4) Skouen JS, Smith AJ, Warrington NM, O' Sullivan PB, McKenzie L, Pennell CE, Straker LM
Genetic variation in the beta-2 adrenergic receptor is associated with chronic musculoskeletal complaints in adolescents.
Eur J Pain. 2012 Mar 13;
BACKGROUND: There is significant evidence to suggest that psychological and stress-related factors are important predictors of the onset of chronic widespread pain (CWP) and fibromyalgia (FM). The hypothalamic-pituitary-adrenal axis, together with the efferent sympathetic/adrenomedullary system, influence all body organs (including muscles) during short- and long-term threatening stimuli. The aim of this study was to investigate the relationship between genetic variants in adrenergic candidate genes and chronic musculoskeletal complaints (MSCs) in adolescents. METHODS: Adolescents from the Western Australian Pregnancy (Raine) Cohort attending the 17-year cohort review completed a questionnaire containing a broad range of psychosocial factors and pain assessment (n?=?1004). Blood samples were collected for DNA extraction and genotyping. Genotype data was obtained for 14 single nucleotide polymorphisms (SNPs) in two candidate genes - beta-2 adrenergic receptor (ADRB2) and catecholamine-O-methyltransferase (COMT). Haplotypes were reconstructed for all individuals with genotype data. RESULTS AND CONCLUSION: Both female gender and poor mental health were associated with (1) an increased risk for chronic, disabling comorbid neck and low back pain (CDCP); and (2) an increase in the number of areas of pain. Of the 14 SNPs evaluated, only SNP rs2053044 (ADRB2, recessive model) displayed an association with CDCP [odds ratio (OR)?=?2.49; 95% confidence interval (CI)?=?1.25, 4.98; p?=?0.01] and pain in three to four pain areas in the last month (OR?=?1.86; 95% CI?=?1.13, 3.06; p?=?0.02). These data suggest that genetic variants in ADRB2 may be involved in chronic MSCs. [PubMed Citation] [Order full text from Infotrieve]


5) Schmechel DE, Edwards CL
Fibromyalgia, mood disorders, and intense creative energy: A1AT polymorphisms are not always silent.
Neurotoxicology. 2012 Mar 10;
Persons with single copies of common alpha-1-antitrypsin polymorphisms such as S and Z are often considered "silent carriers". Published evidence however supports a complex behavioral phenotype or trait - intense creative energy ("ICE")-associated with A1AT polymorphisms. We now confirm that phenotype and present an association of fibromyalgia syndrome (FMS) and A1AT in a consecutive series of neurological patients. This is a retrospective case control series of 3176 consecutive patients presenting to Duke University Memory Clinic (747 patients) and to regional community-based Caldwell Hospital Neurology and Memory center (2429 patients). Work-up included medical history and examination, psychological evaluation, and genetic analysis. Chronic widespread pain (CWP) or FMS were diagnosed according to clinical guidelines, mostly as secondary diagnoses. Neurological patients carrying A1AT polymorphisms were common (ca 16% prevalence) and carriers had significantly higher use of inhaler and anxiolytic medications. Patients with ICE phenotype had a significantly higher proportion of A1AT polymorphisms (42%) compared to non-ICE patients (13%). Presence of CWP or FMS was common (14-22%) with average age at presentation of 56 years old and mostly female gender (82%). Patients with CWP/FMS had again significantly higher proportion of A1AT polymorphisms (38%) compared to other neurological patients (13%). Patients with anxiety disorders, bipolar I or bipolar II disorders or PTSD also had increased proportion of A1AT polymorphisms and significant overlap with ICE and FMS phenotype. Significant reductions in CWP/FMS prevalence are seen in apolipoprotein E4 carriers and methylene tetrahydrofolate reductase (MTHFR) mutation homozygotes. Since ICE phenotype is reported as a lifelong behavioral attribute, the presumption is that A1AT carriers have fundamental differences in brain development and inflammatory response. In support of this concept is finding those persons reporting a diagnosis of juvenile rheumatoid or idiopathic arthritis (JRA, JIA) had a significantly high proportion of A1AT polymorphisms (63%), suggesting a spectrum for JRA to later FMS presentations. Likewise, persons reporting a history of attention deficit disorder (ADD) had an increased proportion of A1AT polymorphisms (26%) compared to non-ADD persons (13%). Toxic environmental exposures are common (23%) and associated with diagnoses of PSP, PPA, FTD, FTD-PD, PD and ADVD. A1AT carriers were increased in cases of toxic exposure and PSP, PPA and FTD-PD. Our findings support the ICE behavioral phenotype for A1AT polymorphism carriers and the reported association with anxiety and bipolar spectrum disorders. We now extend that phenotype to apparent vulnerability to inflammatory muscle disease in a spectrum from JRA to fibromyalgia (FMS) and specific behavioral subsets of ADD, PTSD, and specific late onset neurological syndromes (FTD-PD and PPA). High and low risk FMS subsets can be defined using A1AT, MTHFR and APOE genotyping. Clinical diagnoses associated with A1AT polymorphisms included fibromyalgia, JRA/JIA, bipolar disorder, PTSD, primary progressive aphasia and FTDPD, but not most Alzheimer Disease subtypes. These results support an extended phenotype for A1AT mutation carriers beyond liver and lung vulnerability to selective advantages: ICE phenotype and disadvantages: fibromyalgia, affective disorders, and selected late onset neurological syndromes. [PubMed Citation] [Order full text from Infotrieve]


6) Furuta A, Suzuki Y, Hayashi N, Egawa S, Yoshimura N
Transient receptor potential A1 receptor-mediated neural cross-talk and afferent sensitization induced by oxidative stress: implication for the pathogenesis of interstitial cystitis/bladder pain syndrome.
Int J Urol. 2012 May;19(5):429-36.
Although the pathogenesis of interstitial cystitis/bladder pain syndrome remains unknown, there is a significant correlation of interstitial cystitis/bladder pain syndrome with other chronic pain disorders, such as irritable bowel syndrome, endometriosis and fibromyalgia syndrome. In this review, we highlight evidence supporting neural cross-talk in the dorsal root ganglia, spinal cord and brain levels, which might play a role in the development of chronic pain disorders through central sensitization. In addition, we focus on transient receptor potential V1 and transient receptor potential A1 as the receptor targets for chronic pain conditions, because transient receptor potential V1 and transient receptor potential A1 act as a nocisensor to mediate not only an afferent signal to the dorsal horn of the spinal cord, but also an efferent signal in the periphery through secretion of inflammatory agents, such as substance P and calcitonin gene-related peptide in nociceptive sensory neurons. Furthermore, peripheral inflammation produces multiple inflammatory mediators that act on their cognate receptors to activate intracellular signal transduction pathways and thereby modify the expression and function of transient receptor potential V1 and transient receptor potential A1 (peripheral sensitization). During tissue damage and inflammation, oxidative stress, such as reactive oxygen species or reactive carbonyl species is also generated endogenously. The highly diffusible nature might account for the actions of free radical formation far from the site of injury, thereby producing systemic pain conditions without central sensitization through neural cross-talk. Because oxidative stress is considered to induce activation of transient receptor potential A1, we also discuss exogenous and endogenous oxidative stress to elucidate its role in the pathogenesis of interstitial cystitis/bladder pain syndrome and other chronic pain conditions. [PubMed Citation] [Order full text from Infotrieve]


7) Vargas-Alarcon G, Alvarez-Leon E, Fragoso JM, Vargas A, Martinez A, Vallejo M, Martinez-Lavin M
A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia.
BMC Musculoskelet Disord. 2012;13:23.
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8) White AT, Light AR, Hughen RW, Vanhaitsma TA, Light KC
Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls.
Psychosom Med. 2012 Jan;74(1):46-54.
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9) Mergener M, Becker RM, dos Santos AF, dos Santos GA, de Andrade FM
Influence of the interaction between environmental quality and T102C SNP in the HTR2A gene on fibromyalgia susceptibility.
Rev Bras Reumatol. 2011 Dec;51(6):594-602.
[PubMed Citation] [Order full text from Infotrieve]


10) Light KC, White AT, Tadler S, Iacob E, Light AR
Genetics and Gene Expression Involving Stress and Distress Pathways in Fibromyalgia with and without Comorbid Chronic Fatigue Syndrome.
Pain Res Treat. 2012;2012:427869.
In complex multisymptom disorders like fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) that are defined primarily by subjective symptoms, genetic and gene expression profiles can provide very useful objective information. This paper summarizes research on genes that may be linked to increased susceptibility in developing and maintaining these disorders, and research on resting and stressor-evoked changes in leukocyte gene expression, highlighting physiological pathways linked to stress and distress. These include the adrenergic nervous system, the hypothalamic-pituitary-adrenal axis and serotonergic pathways, and exercise responsive metabolite-detecting ion channels. The findings to date provide some support for both inherited susceptibility and/or physiological dysregulation in all three systems, particularly for catechol-O-methyl transferase (COMT) genes, the glucocorticoid and the related mineralocorticoid receptors (NR3C1, NR3C2), and the purinergic 2X4 (P2X4) ion channel involved as a sensory receptor for muscle pain and fatigue and also in upregulation of spinal microglia in chronic pain models. Methodological concerns for future research, including potential influences of comorbid clinical depression and antidepressants and other medications, on gene expression are also addressed. [PubMed Citation] [Order full text from Infotrieve]


11) Elfaitouri A, Shao X, Mattsson Ulfstedt J, Muradrasoli S, Bölin Wiener A, Golbob S, Ohrmalm C, Matousek M, Zachrisson O, Gottfries CG, Blomberg J
Murine gammaretrovirus group G3 was not found in Swedish patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia.
PLoS One. 2011;6(10):e24602.
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12) Leehey MA, Legg W, Tassone F, Hagerman R
Fibromyalgia in fragile X mental retardation 1 gene premutation carriers.
Rheumatology (Oxford). 2011 Dec;50(12):2233-6.
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13) Smith SB, Maixner DW, Fillingim RB, Slade G, Gracely RH, Ambrose K, Zaykin DV, Hyde C, John S, Tan K, Maixner W, Diatchenko L
Large candidate gene association study reveals genetic risk factors and therapeutic targets for fibromyalgia.
Arthritis Rheum. 2012 Feb;64(2):584-93.
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14) Desmeules J, Piguet V, Besson M, Chabert J, Rapiti E, Rebsamen M, Rossier MF, Curtin F, Dayer P, Cedraschi C
Psychological distress in fibromyalgia patients: a role for catechol-O-methyl-transferase Val158met polymorphism.
Health Psychol. 2012 Mar;31(2):242-9.
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15) Holliday KL, McBeth J
Recent advances in the understanding of genetic susceptibility to chronic pain and somatic symptoms.
Curr Rheumatol Rep. 2011 Dec;13(6):521-7.
Regional (e.g., low back) and widespread chronic pain disorders are common in the general population and are known to be heritable. Recent research suggests that genetic factors increase the risk of developing chronic pain independent of the site of pain. Candidate gene studies have been conducted on key pathways to elucidate susceptibility genes that are likely to be involved in both the sensory and affective components of pain. Findings have been largely equivocal, predominantly due to small sample size, but larger studies of pain in general population samples are being conducted. Interesting candidate genes from animal models and monogenic pain disorders are beginning to emerge. Recent advances in genetics research have yet to make an impact in the pain field but provide considerable scope for future research efforts. [PubMed Citation] [Order full text from Infotrieve]


16) De Luca C, Raskovic D, Pacifico V, Thai JC, Korkina L
The search for reliable biomarkers of disease in multiple chemical sensitivity and other environmental intolerances.
Int J Environ Res Public Health. 2011 Jul;8(7):2770-97.
Whilst facing a worldwide fast increase of food and environmental allergies, the medical community is also confronted with another inhomogeneous group of environment-associated disabling conditions, including multiple chemical sensitivity (MCS), fibromyalgia, chronic fatigue syndrome, electric hypersensitivity, amalgam disease and others. These share the features of poly-symptomatic multi-organ cutaneous and systemic manifestations, with postulated inherited/acquired impaired metabolism of chemical/physical/nutritional xenobiotics, triggering adverse reactions at exposure levels far below toxicologically-relevant values, often in the absence of clear-cut allergologic and/or immunologic involvement. Due to the lack of proven pathogenic mechanisms generating measurable disease biomarkers, these environmental hypersensitivities are generally ignored by sanitary and social systems, as psychogenic or "medically unexplained symptoms". The uncontrolled application of diagnostic and treatment protocols not corresponding to acceptable levels of validation, safety, and clinical efficacy, to a steadily increasing number of patients demanding assistance, occurs in many countries in the absence of evidence-based guidelines. Here we revise available information supporting the organic nature of these clinical conditions. Following intense research on gene polymorphisms of phase I/II detoxification enzyme genes, so far statistically inconclusive, epigenetic and metabolic factors are under investigation, in particular free radical/antioxidant homeostasis disturbances. The finding of relevant alterations of catalase, glutathione-transferase and peroxidase detoxifying activities significantly correlating with clinical manifestations of MCS, has recently registered some progress towards the identification of reliable biomarkers of disease onset, progression, and treatment outcomes. [PubMed Citation] [Order full text from Infotrieve]


17) Altinoz MA, Gedikoglu G, Deniz G
β-Thalassemia trait association with autoimmune diseases: β-globin locus proximity to the immunity genes or role of hemorphins?
Immunopharmacol Immunotoxicol. 2012 Apr;34(2):181-90.
Thalassemia major continues to be a significant health problem for Mediterranean, Afro-Arabic countries, India and South Easth Asia. It was generally assumed that the ?-thalassemia heterozygotes do not bear significant medical risks except a mild microcytic anemia. Nonetheless, increasing number of reports associate ?-thalassemia trait with autoimmune conditions, nephritis, diabetes, arthritis, fibromyalgia and asthma. Available sparse data indicate reduced incidence of systemic lupus erythematosus (SLE) in ?-thalassemia heterozygotes; yet, if two conditions coexist, the SLE manifestations occur much severer. These associations make sense when considering that the hemoglobin ?-chain locus at 11p15.5 resides in close proximity to eight genes with profound roles in immune regulation: STIM1, CD151, TC21/RRAS2, SIGIRR/TOLL/IL1R8, pp52/LSP1 (lymphocyte specific protein), TRIM21, toll interacting protein (TOLLIP) and SLEN3. ?-Thalassemia trait accompaniment to autoimmune disease may be the result of haplotypal associations between the close proximity genes. An alternative explanation to thalassemia heterozygosity: autoimmune disease association may be the changed concentrations of hemorphins. Hemorphins are endogenous opioid peptides derived via proteolytical cleavage of hemoglobin. They are shown to bind diverse opioid receptors and act anti-inflammatory. Their reduced expression in thalassemia heterozygosity may explain a proinflammatory stage and autoimmunity vulnerability. [PubMed Citation] [Order full text from Infotrieve]


18) Xiao Y, Russell IJ, Liu YG
A brain-derived neurotrophic factor polymorphism Val66Met identifies fibromyalgia syndrome subgroup with higher body mass index and C-reactive protein.
Rheumatol Int. 2012 Aug;32(8):2479-85.
A common single nucleotide polymorphism (SNP) in the gene of brain-derived neurotrophic factor (BDNF) results from a substitution at position 66 from valine (Val) to methionine (Met) and may predispose to human neuropsychiatric disorders. We proposed to determine whether these BDNF gene SNPs were associated with fibromyalgia syndrome (FMS) and/or any of its typical phenotypes. Patients with FMS (N = 95) and healthy normal controls (HNC, N = 58) were studied. Serum high-sensitivity C-reactive protein (hsCRP) levels were measured using an enzyme-linked immunosorbent assay (ELISA). The BDNF SNPs were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The BDNF SNP distribution was 65 (68%) Val/Val, 28 (30%) Val/Met, and 2 (2%) Met/Met for FMS and 40 (69%), 17(29%), and 1 (2%) for HNC, respectively. The serum high-sensitivity C-reactive protein (hsCRP)and body mass index (BMI) in FMS were higher than in HNC. The FMS with BDNF Val66Val had significantly higher mean BMI (P = 0.0001) and hsCRP (P = 0.02) than did FMS carrying the Val66Met genotype. This pattern was not found in HNC. Phenotypic measures of subjective pain, pain threshold, depression, or insomnia did not relate to either of the BDNF SNPs in FMS. The relative distribution BDNF SNPs did not differ between FMS and HNC. The BDNF Val66Met polymorphism is not selective for FMS. The BDNF Val66Val SNP identifies a subgroup of FMS with elevated hsCRP and higher BMI. This is the first study to associate a BDNF polymorphism with a FMS subgroup phenotype. [PubMed Citation] [Order full text from Infotrieve]


19) Gupta S, McCarson KE, Welch KM, Berman NE
Mechanisms of pain modulation by sex hormones in migraine.
Headache. 2011 Jun;51(6):905-22.
A number of pain conditions, acute as well as chronic, are much more prevalent in women, such as temporomandibular disorder (TMD), irritable bowel syndrome, fibromyalgia, and migraine. The association of female sex steroids with these nociceptive conditions is well known, but the mechanisms of their effects on pain signaling are yet to be deciphered. We reviewed the mechanisms through which female sex steroids might influence the trigeminal nociceptive pathways with a focus on migraine. Sex steroid receptors are located in trigeminal circuits, providing the molecular substrate for direct effects. In addition to classical genomic effects, sex steroids exert rapid nongenomic actions to modulate nociceptive signaling. Although there are only a handful of studies that have directly addressed the effect of sex hormones in animal models of migraine, the putative mechanisms can be extrapolated from observations in animal models of other trigeminal pain disorders, like TMD. Sex hormones may regulate sensitization of trigeminal neurons by modulating expression of nociceptive mediator such as calcitonin gene-related peptide. Its expression is mostly positively regulated by estrogen, although a few studies also report an inverse relationship. Serotonin (5-Hydroxytryptamine [5-HT]) is a neurotransmitter implicated in migraine; its synthesis is enhanced in most parts of brain by estrogen, which increases expression of the rate-limiting enzyme tryptophan hydroxylase and decreases expression of the serotonin re-uptake transporter. Downstream signaling, including extracellular signal-regulated kinase activation, calcium-dependent mechanisms, and cAMP response element-binding activation, are thought to be the major signaling events affected by sex hormones. These findings need to be confirmed in migraine-specific animal models that may also provide clues to additional ion channels, neuropeptides, and intracellular signaling cascades that contribute to the increased prevalence of migraine in women. [PubMed Citation] [Order full text from Infotrieve]


20) Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC
Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome.
J Intern Med. 2012 Jan;271(1):64-81.
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