中国人群中瞬时受体电位（TRP）通道与谷氨酸能突触基因多态性与偏头痛及共病焦虑和抑郁之间的关联

Association between TRP channels and glutamatergic synapse gene polymorphisms and migraine and the comorbidities anxiety and depression in a Chinese population.

作者信息

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

机构信息

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.

出版信息

Front Genet. 2023 May 26;14:1158028. doi: 10.3389/fgene.2023.1158028. eCollection 2023.

DOI:10.3389/fgene.2023.1158028

PMID:37303955

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10250607/

Abstract

Genetic and environmental factors contribute to migraine and the comorbidities of anxiety and depression. However, the association between genetic polymorphisms in the transient receptor potential (TRP) channels and glutamatergic synapse genes with the risk of migraine and the comorbidities of anxiety and depression remain unclear. 251 migraine patients containing 49 comorbidities with anxiety and 112 with depression and 600 controls were recruited. A customized 48-plex SNPscan kit was used for genotyping 13 SNPs of nine target genes. Logistic regression was conducted to analyze these SNPs' association with the susceptibility of migraine and comorbidities. The generalized multifactor dimension reduction (GMDR) was applied to analyze the SNP-SNP and gene-environment interactions. The GTEx database was used to examine the effects of the significant SNPs on gene expressions. The rs8065080 and rs7217270 were associated with an increased risk of migraine in the dominant model [OR (95% CI): 1.75 (1.09-2.90), = 0.025; 1.63 (1.02-2.58), = 0.039, respectively]. rs2227283 was associated with migraine in the edge of significance [OR (95% CI) = 1.36 (0.99-1.89), = 0.062]. In migraine patients, rs222741 was associated with both anxiety risk and depression risk in the recessive model [OR (95% CI): 2.64 (1.24-5.73), = 0.012; 1.97 (1.02-3.85), = 0.046, respectively]. rs7577262 was associated with anxiety (OR = 0.27, 95% CI = 0.10-0.76, = 0.011). rs3742037, rs17862920 and rs11110359 were associated with depression in dominant model [OR (95% CI): 2.03 (1.06-3.96), = 0.035; 0.48 (0.23-0.96), = 0.042; 0.42 (0.20-0.84), = 0.016, respectively]. Significant eQTL and sQTL signals were observed for SNP rs8065080. Individuals with GRS (Genetic risk scores) of Q4 (14-17) had a higher risk of migraine and a lower risk of comorbidity anxiety than those with Genetic risk scores scores of Q1 (0-9) groups [OR (95% CI): 2.31 (1.39-3.86), = 0.001; 0.28 (0.08-0.88), = 0.034, respectively]. This study suggests that rs8065080, rs7217270, and rs2227283 polymorphism may associate with migraine risk. rs222741 and rs7577262 may associate with migraine comorbidity anxiety risk. rs222741, rs3742037, rs17862920, and rs11110359 may associate with migraine comorbidity depression risk. Higher GRS scores may increase migraine risk and decrease comorbidity anxiety risk.

摘要

遗传和环境因素导致偏头痛以及焦虑和抑郁共病。然而，瞬时受体电位（TRP）通道和谷氨酸能突触基因中的基因多态性与偏头痛风险以及焦虑和抑郁共病之间的关联仍不清楚。招募了251名偏头痛患者，其中49名伴有焦虑共病，112名伴有抑郁共病，以及600名对照。使用定制的48重SNPscan试剂盒对9个靶基因的13个单核苷酸多态性（SNP）进行基因分型。进行逻辑回归分析这些SNP与偏头痛易感性和共病的关联。应用广义多因素降维法（GMDR）分析SNP-SNP和基因-环境相互作用。使用GTEx数据库检查显著SNP对基因表达的影响。rs8065080和rs7217270在显性模型中与偏头痛风险增加相关[比值比（95%可信区间）：分别为1.75（1.09至2.90），P = 0.025；1.63（1.02至2.58），P = 0.039]。rs2227283在显著性边缘与偏头痛相关[比值比（95%可信区间）= 1.36（0.99至1.89），P = 0.062]。在偏头痛患者中，rs222741在隐性模型中与焦虑风险和抑郁风险均相关[比值比（95%可信区间）：分别为2.64（1.24至5.73），P = 0.012；1.97（1.02至3.85），P = 0.046]。rs7577262与焦虑相关（比值比 = 0.27，95%可信区间 = 0.10至0.76，P = 0.011）。rs3742037、rs17862920和rs11110359在显性模型中与抑郁相关[比值比（95%可信区间）：分别为2.03（1.06至3.96），P = 0.035；0.48（0.23至0.96），P = 0.042；0.42（0.20至0.84），P = 0.016]。观察到SNP rs8065080有显著的表达数量性状基因座（eQTL）和剪接数量性状基因座（sQTL）信号。遗传风险评分（GRS）为Q4（14至17）的个体比遗传风险评分为Q1（0至9）组的个体有更高的偏头痛风险和更低的共病焦虑风险[比值比（95%可信区间）：分别为2.31（1.39至3.86），P = 0.001；0.28（0.08至0.88），P = 0.034]。本研究表明，rs8065080、rs7217270和rs2227283多态性可能与偏头痛风险相关。rs222741和rs7577262可能与偏头痛共病焦虑风险相关。rs222741、rs3742037、rs17862920和rs11110359可能与偏头痛共病抑郁风险相关。更高的GRS评分可能增加偏头痛风险并降低共病焦虑风险。