Association between MAPK and PI3K/Akt signaling pathway-related gene polymorphisms and migraine

Background The causes of migraine remain unclear. Evidence suggests that the MAPK and PI3K/Akt signaling pathways play a role in migraine pathogenesis. However, studies on genetic polymorphisms in the two pathways associated with migraine are still limited. Methods This study included 226 migraineurs and 452 age- and sex-matched nonmigraine control individuals. Genotyping of 31 Single Nucleotide Polymorphisms (SNPs) in 21 genes was performed. The relationship between migraine and gene polymorphisms was analyzed by using logistic regression. SNP-SNP interactions were examined by a generalized multifactor dimension reduction (GMDR) approach. The possible role of SNPs was evaluated with gene expression data from the GTEx database. Results The RASGRP2-rs2230414 GT genotype was associated with decreased migraine risk compared with the wild-type GG genotype [ORadj (95% CI): 0.674(0.458-0.989)]. PIK3R1-rs3730089 was associated with migraine in the recessive model [ORadj (95% CI): 1.446(1.004-2.083)]. The CACNA1H-rs61734410 CT genotype was associated with migraine risk [ORadj (95% CI): 1.561(1.068-2.281)]. One significant two-way SNP-SNP interaction was found (PRKCA rs2228945-BDNF rs6265) (p = 0.0107). Significant eQTL and sQTL signals were observed for the SNP rs2230414. Conclusions This is the first study to systematically reveal significant associations between MAPK and PI3K/Akt signaling pathway-related gene polymorphisms and migraine risk. This is the first systematic study to assess the association between polymorphisms of MAPK and PI3K/Akt signaling pathway-related genes and the risk of migraine susceptibility.image