Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, China.
Chronic Disease Prevention and Treatment Clinic, Heilongjiang Provincial Center for Disease Control and Prevention, Harbin, China.
Mol Genet Genomic Med. 2024 Aug;12(8):e2503. doi: 10.1002/mgg3.2503.
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.
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.
The RASGRP2-rs2230414 GT genotype was associated with decreased migraine risk compared with the wild-type GG genotype [OR (95% CI): 0.674(0.458-0.989)]. PIK3R1-rs3730089 was associated with migraine in the recessive model [OR (95% CI): 1.446(1.004-2.083)]. The CACNA1H-rs61734410 CT genotype was associated with migraine risk [OR (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.
This is the first study to systematically reveal significant associations between MAPK and PI3K/Akt signaling pathway-related gene polymorphisms and migraine risk.
偏头痛的病因仍不清楚。有证据表明，MAPK 和 PI3K/Akt 信号通路在偏头痛发病机制中起作用。然而，关于这两条通路中与偏头痛相关的遗传多态性的研究仍然有限。
本研究纳入了 226 名偏头痛患者和 452 名年龄和性别匹配的非偏头痛对照个体。对 21 个基因中的 31 个单核苷酸多态性（SNP）进行基因分型。采用逻辑回归分析偏头痛与基因多态性的关系。采用广义多因子降维（GMDR）方法分析 SNP-SNP 相互作用。利用 GTEx 数据库中的基因表达数据评估 SNP 的可能作用。
与野生型 GG 基因型相比，RASGRP2-rs2230414 GT 基因型与偏头痛风险降低相关[比值比（95%可信区间）：0.674（0.458-0.989）]。PIK3R1-rs3730089 在隐性模型中与偏头痛相关[比值比（95%可信区间）：1.446（1.004-2.083）]。CACNA1H-rs61734410 CT 基因型与偏头痛风险相关[比值比（95%可信区间）：1.561（1.068-2.281）]。发现一个显著的双向 SNP-SNP 相互作用（PRKCA rs2228945-BDNF rs6265）（p=0.0107）。SNP rs2230414 存在显著的 eQTL 和 sQTL 信号。
这是第一项系统揭示 MAPK 和 PI3K/Akt 信号通路相关基因多态性与偏头痛风险之间显著关联的研究。
