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

Mingxue Wang1, Yujia Gu2, Shuhan Meng1

  • 1Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, China.

Molecular Genetics & Genomic Medicine
|August 14, 2024
PubMed
Abstract

Insights

Genetic variations in MAPK and PI3K/Akt pathways are linked to migraine. This study identified specific gene polymorphisms associated with altered migraine risk, offering new insights into its pathogenesis.

Area of Science:

  • Genetics
  • Neurology
  • Molecular Biology

Background:

  • Migraine pathogenesis is not fully understood.
  • Mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways are implicated in migraine.
  • Limited research exists on the association between genetic polymorphisms in these pathways and migraine.

Purpose of the Study:

  • To investigate the association between genetic polymorphisms in MAPK and PI3K/Akt signaling pathway genes and migraine risk.
  • To explore gene-gene interactions and their impact on migraine susceptibility.

Main Methods:

  • Case-control study with 226 migraineurs and 452 controls.
  • Genotyping of 31 single nucleotide polymorphisms (SNPs) in 21 relevant genes.
  • Logistic regression analysis for SNP-migraine association and generalized multifactor dimension reduction (GMDR) for SNP-SNP interactions.
  • Evaluation of SNP function using gene expression data from the Genotype-Tissue Expression (GTEx) database.

Main Results:

  • RASGRP2-rs2230414 polymorphism was associated with reduced migraine risk.
  • PIK3R1-rs3730089 and CACNA1H-rs61734410 polymorphisms were associated with increased migraine risk.
  • A significant two-way interaction was found between PRKCA rs2228945 and BDNF rs6265.
  • Expression quantitative trait locus (eQTL) and splice quantitative trait locus (sQTL) signals were observed for rs2230414.

Conclusions:

  • This study provides the first systematic evidence linking polymorphisms in MAPK and PI3K/Akt signaling pathway genes to migraine risk.
  • Identified SNPs and their interactions may contribute to migraine susceptibility.
  • Findings offer potential targets for understanding migraine pathophysiology.
Keywords:
MAPKPI3K/Aktmigrainesignaling pathwaysingle nucleotide polymorphism

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