Fibromyalgia (FM) is a syndrome of unknown aetiology characterised by chronic wide spread pain, increased tenderness to palpation and additional symptoms such as disturbed sleep, stiffness, fatigue and psychological distress. Familial aggregation of FM is common. Depressive symptoms and psychological distress is a frequent finding in FM patients and their relatives.1 These findings suggest that genetic and familial factors may play a role in the etiopathogenesis of this syndrome. In a recent linkage analysis of 40 FM multicase families it was shown that the HLA region might be a candidate for genetic transmission of vulnerability for the disorder.2
The pathophysiological mechanisms underlying fibromyalgia have been linked to disturbances in serotonin (5-HT) metabolism and transmission. Among the different parameters of the serotonin pathway the genes coding for the 5-HT receptors and transporters are interesting candidates to investigate a genetically driven predisposition to FM. Recent studies have analysed silent and functional polymorphic variants of these genes in patients with fibromyalgia:3,4,5
The human 5-HT transporter (5-HTT) is encoded by a single gene on chromosome 17q12. A functional polymorphism in the transcriptional region has been described (“long allele” L or “short allele” S). In a study of 62 FM patients a higher frequency of the S/S genotype of the 5-HTT was found compared to healthy controls. The S/S subgroup revealed higher means in depression and psychological distress.
The 5-HT2A receptor gene is located on chromosome 13q14–21. A silent T102C polymorphism of the 5-HT2A receptor gene has recently been detected. In a sample of 168 FM patients a statistically significant different distribution of genotypes was found with a decrease in T/T and an increase in both T/C and C/C gentotypes compared to controls. A correlation of genotypes with pain variables revealed higher scores in the tenderpoints score in patients with the T/T genotype. Correlations with psychopathological symptoms were not significant.
The 5-HT2C receptor gene is located on the X chromosome. In a sample of 65 FM patients the presence of the 5-HT2C (C32S) mutant was significantly correlated with measures of psychological distress. In the same sample the tryptophan hydroxylase (TPH) gene was analysed. The TPH gene is located on the short arm of chromosome 11 and a polymorphism in intron 7 has recently been detected. The TPH is the rate limiting enzyme that determines the concentrations of serotonin in vivo. No significant different frequencies of the allels were found in this group of FM patients compared to control subjects.
The implication of these findings for the etiopathogensis of fibromyalgia is far from clear and have to be replicated in larger and ethnical different samples. But these results might point to a disturbance on 5-HT-receptor and transporter level at least in a subgroup of FM patients and emphasises the importance of the serotonergic system in the pathophysiology of FM.
Offenbaecher M, Glatzeder K, Ackenheil M. Self reported depression, familial history of depression, fibromyalgia (FM) and psychological distress in patients with FM. Z Rheumatol. 1998;57:94–6
Yunus MB, Khan MA, Rawlings KK, Green JR, Olson JM, Shah S. Genetic linkage analysis of multicase families with fibromyalgia syndrome. J Rheumatol 1999;26:408–12
Offenbaecher M, Bondy B, de Jonge S, Glatzeder K, Krueger M, Schoeps P, Ackenheil M. Possible association of fibromyalgia with a polymorphismus in the serotonin transporter gene regulatory region. Arthritis Rheum 1999;42:2482–8
Bondy B, Spaeth M, Offenbaecher M, Glatzeder K, Stratz T, Schwarz M, de Jonge S, Krüger M, Engel R, Faerber L, Pongratz D, Ackenheil M. The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia. Neurobiol Dis. 1999;6:433–9
Offenbaecher M, Bondy B, de Jonge S, Glatzeder K, Behrens S, Schoeps P, Ackenheil M. Evidence for involvement of 5-HT2a and 5-HT2c receptor genes in fibromyalgia. Poster presented at the 9th world congress on pain, 1999
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