解析 rs2651899、rs10166942 和 rs11172113 多态性在偏头痛中的作用:一项荟萃分析。

Deciphering the Role of the rs2651899, rs10166942, and rs11172113 Polymorphisms in Migraine: A Meta-Analysis.

机构信息

Laboratory of Neurogenetics, Department of Neurology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41100 Larissa, Greece.

Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece.

出版信息

Medicina (Kaunas). 2022 Mar 29;58(4):491. doi: 10.3390/medicina58040491.

Abstract

The genetic basis of migraine is rather complex. The rs2651899 in the PR/SET domain 16 (PRDM16) gene, the rs10166942 near the transient receptor potential cation channel subfamily M member 8 (TRPM8) gene, and the rs11172113 in the LDL receptor-related protein 1 (LRP1) gene, have been associated with migraine in a genome-wide association study (GWAS). However, data from subsequent studies examining the role of these variants and their relationship with migraine remain inconclusive. The aim of the present study was to meta-analyze the published data assessing the role of these polymorphisms in migraine, migraine with aura (MA), and migraine without aura (MO). We performed a search in the PubMed, Scopus, Web of Science, and Public Health Genomics and Precision Health Knowledge Base (v7.7) databases. In total, eight, six, and six studies were included in the quantitative analysis, for the rs2651899, rs10166942, and rs11172113, respectively. Cochran’s Q and I2 tests were used to calculate the heterogeneity. The random effects (RE) model was applied when high heterogeneity was observed; otherwise, the fixed effects (FE) model was applied. The odds ratios (ORs) and the respective 95% confidence intervals (CIs) were calculated to estimate the effect of each variant on migraine. Funnel plots were created to graphically assess publication bias. A significant association was revealed for the CC genotype of the rs2651899, with the overall migraine group (RE model OR: 1.32; 95% CI: 1.02−1.73; p-value = 0.04) and the MA subgroup (FE model OR: 1.40; 95% CI: 1.12−1.74; p-value = 0.003). The rs10166942 CT genotype was associated with increased migraine risk (FE model OR: 1.36; 95% CI: 1.18−1.57; p-value < 0.0001) and increased MO risk (FE model OR: 1.41; 95% CI: 1.17−1.69; p-value = 0.0003). No association was detected for the rs11172113. The rs2651899 and the rs10166942 have an effect on migraine. Larger studies are needed to dissect the role of these variants in migraine.

摘要

偏头痛的遗传基础相当复杂。在全基因组关联研究(GWAS)中,PR/SET 结构域 16(PRDM16)基因中的 rs2651899、瞬时受体电位阳离子通道亚家族 M 成员 8(TRPM8)基因附近的 rs10166942 以及 LDL 受体相关蛋白 1(LRP1)基因中的 rs11172113 与偏头痛有关。然而,随后研究这些变体的作用及其与偏头痛关系的数据仍不确定。本研究的目的是对评估这些多态性在偏头痛、有先兆偏头痛(MA)和无先兆偏头痛(MO)中的作用的已发表数据进行荟萃分析。我们在 PubMed、Scopus、Web of Science 和公共卫生基因组学和精准健康知识库(v7.7)数据库中进行了搜索。分别有八项、六项和六项研究纳入了 rs2651899、rs10166942 和 rs11172113 的定量分析。使用 Cochran’s Q 和 I2 检验计算异质性。当观察到高度异质性时,采用随机效应(RE)模型;否则,采用固定效应(FE)模型。计算比值比(ORs)和相应的 95%置信区间(CIs),以估计每个变体对偏头痛的影响。绘制漏斗图以直观评估发表偏倚。rs2651899 的 CC 基因型与总体偏头痛组(RE 模型 OR:1.32;95%CI:1.02-1.73;p 值=0.04)和 MA 亚组(FE 模型 OR:1.40;95%CI:1.12-1.74;p 值=0.003)显著相关。rs10166942 的 CT 基因型与偏头痛风险增加相关(FE 模型 OR:1.36;95%CI:1.18-1.57;p 值<0.0001)和 MO 风险增加相关(FE 模型 OR:1.41;95%CI:1.17-1.69;p 值=0.0003)。rs11172113 未检测到相关性。rs2651899 和 rs10166942 对偏头痛有影响。需要更大的研究来剖析这些变体在偏头痛中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/064b/9031971/27976d3b15c9/medicina-58-00491-g001.jpg

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