Candidate gene studies of fibromyalgia: a systematic review and meta-analysis

The aim of this study was to explore whether the candidate gene polymorphisms contribute to fibromyalgia susceptibility. The authors conducted a meta-analysis on associations between serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) S/L allele, catechol-O-methltransferase (COMT) val158Met, and serotonin 2A (5-HT2A) receptor 102T/C polymorphisms and fibromyalgia susceptibility as determined using the following: (1) allele contrast, (2) recessive, (3) dominant models, and (4) contrast of homozygotes. We also performed a systematic review with available data of the candidate genes. A total of 21 separate comparisons were considered in this systematic review and meta-analysis. Seventeen candidate genes and over 35 different polymorphisms were identified in studies on fibromyalgia susceptibility. Meta-analysis of the 5-HTTLPR S/L allele and COMT val158Met failed to reveal any association with fibromyalgia. However, meta-analysis of the C allele, CC + CT genotype, and CC versus TT genotype of the 5-HT2A receptor 102T/C polymorphism showed significant association with fibromyalgia. The overall OR of the association between the C allele and fibromyalgia was 1.333 (95% CI = 1.053-1.688, P = 0.017). The ORs for the CC + CT genotype, and CC versus TT genotype showed the same pattern as that observed for the C allele (OR = 1.541, 95% CI = 1.032-2.303, P = 0.035; OR = 1.838, 95% CI = 1.151-2.936, P = 0.011). This meta-analysis demonstrates that the 5-HT2A receptor 102T/C polymorphism confers susceptibility to fibromyalgia. In contrast, no association was found between the 5-HTTLPR S/L allele, COMT val158Met, and susceptibility to fibromyalgia.