{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T23:25:32Z","timestamp":1791761132580,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study included 226 migraineurs and 452 age\u2010 and sex\u2010matched 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\u2013SNP 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:italic>RASGRP2<\/jats:italic>\u2010rs2230414 GT genotype was associated with decreased migraine risk compared with the wild\u2010type GG genotype [OR<jats:sub>adj<\/jats:sub> (95% CI): 0.674(0.458\u20130.989)]. <jats:italic>PIK3R1<\/jats:italic>\u2010rs3730089 was associated with migraine in the recessive model [OR<jats:sub>adj<\/jats:sub> (95% CI): 1.446(1.004\u20132.083)]. The <jats:italic>CACNA1H<\/jats:italic>\u2010rs61734410 CT genotype was associated with migraine risk [OR<jats:sub>adj<\/jats:sub> (95% CI): 1.561(1.068\u20132.281)]. One significant two\u2010way SNP\u2013SNP interaction was found (<jats:italic>PRKCA<\/jats:italic> rs2228945\u2010<jats:italic>BDNF<\/jats:italic> rs6265) (<jats:italic>p<\/jats:italic>\u2009=\u20090.0107). Significant eQTL and sQTL signals were observed for the SNP rs2230414.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the first study to systematically reveal significant associations between MAPK and PI3K\/Akt signaling pathway\u2010related gene polymorphisms and migraine risk.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2503","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T12:48:50Z","timestamp":1723639730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Association between <scp>MAPK<\/scp> and <scp>PI3K<\/scp>\/Akt signaling pathway\u2010related gene polymorphisms and migraine"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8002-5206","authenticated-orcid":false,"given":"Mingxue","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Epidemiology, School of Public Health Harbin 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