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

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Molecular Genetics & Genomic Medicine Pub Date : 2024-08-01 DOI:10.1002/mgg3.2503

Mingxue Wang, Yujia Gu, Shuhan Meng, Lixin Kang, Jing Yang, Degang Sun, Yuxing Liu, Ze Wan, Yi Shan, Dongjie Xue, Chang Su, Shufen Li, RanYan, Yu Liu, Yonghui Pan, Yashuang Zhao

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引用次数: 0

Abstract

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 [OR_adj (95% CI): 0.674(0.458-0.989)]. PIK3R1-rs3730089 was associated with migraine in the recessive model [OR_adj (95% CI): 1.446(1.004-2.083)]. The CACNA1H-rs61734410 CT genotype was associated with migraine risk [OR_adj (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.

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MAPK和PI3K/Akt信号通路相关基因多态性与偏头痛之间的关系。

背景：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发挥作用。然而，有关这两条途径中与偏头痛相关的基因多态性的研究仍然有限：本研究包括 226 名偏头痛患者和 452 名年龄和性别匹配的非偏头痛对照者。对 21 个基因中的 31 个单核苷酸多态性（SNPs）进行了基因分型。利用逻辑回归分析了偏头痛与基因多态性之间的关系。采用广义多因素降维（GMDR）方法研究了SNP-SNP之间的相互作用。利用 GTEx 数据库中的基因表达数据评估了 SNP 的可能作用：结果：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[ORadj (95% CI)：0.674(0.458-0.989)]。在隐性模型中，PIK3R1-rs3730089 与偏头痛相关[ORadj (95% CI)：1.446(1.004-2.083)]。CACNA1H-rs61734410 CT 基因型与偏头痛风险相关[ORadj (95% CI)：1.561(1.068-2.281)]。发现了一个显着的 SNP-SNP 双向交互作用（PRKCA rs2228945-BDNF rs6265）（p = 0.0107）。在 SNP rs2230414 上观察到了显著的 eQTL 和 sQTL 信号：这是首次系统揭示 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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.20

自引率

0.00%

发文量

241

审稿时长

14 weeks

期刊介绍： Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.