Association of 5-HTT gene polymorphisms with migraine: A systematic review and meta-analysis

Background/aims: Serotonin is known to play an important role in the pathogenesis of migraine, but individual genetic association studies that examine the relationship between polymorphisms of serotonin transporter (5-HTT) gene and migraine have yielded inconsistent results. This study aimed to evaluate the association between 5-HTT gene variants (including 5-HTTLPR, VNTR and SNP) and migraine using systematic review with meta-analysis. Methods: Relevant studies were identified by searching English and Chinese databases extensively. Allele and genotype frequencies for each included study were extracted. The odds ratio (OR) was calculated using a random-effects or fixed-effects model. Q statistic was used to evaluate homogeneity, and Egger's test and Funnel plot were used to assess publication bias. For family-based association studies, a descriptive analysis was carried out. Results: A total of 15 studies were identified for meta-analysis. It was found that the 5-HTT VNTR Stin2.12 allele or 12/12 genotype had an increased risk for migraine in the general population (Stin2.12 allele: OR, 95% CI: 1.34, 1.09-1.64, p = 0.006; 12/12 genotype: OR, 95% CI: 1.55, 1.17-2.05, p = 0.002), but there was no significant association between migraine and 5-HTTLPR or SNP rs2020942. Conclusions: Existing evidence indicates that the 5-HTT VNTR polymorphism (mainly the STin2.12 genotype) is associated with an increased risk of migraine in the general population. Future studies with larger sample sizes will be necessary to confirm the present results.