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BIN1和GAB2基因与阿尔茨海默病的关联:一项荟萃分析和系统评价

Genetic association of BIN1 and GAB2 in Alzheimer's disease: A meta-analysis and systematic review.

作者信息

Hao Xiaoyan, Wang Aijun, Li Chong, Shao Lufei, Li Yi, Yang Ping

机构信息

Department of Neurology, Ningxia Medical University, Yinchuan, China.

Department of Neurology, General Hospital of Ningxia Medical University, Yinchuan, China.

出版信息

Geriatr Gerontol Int. 2021 Feb;21(2):185-191. doi: 10.1111/ggi.14109. Epub 2020 Dec 16.

Abstract

AIM

Heredity plays an important role in the pathogenesis of Alzheimer's disease (AD) especially for single-nucleotide polymorphism (SNPs) of susceptible genes, which is one of the significant factors in the pathogenesis of AD. The SNPs of BIN1 rs744373, BIN1 rs7561528 and GAB2 rs2373115 are associated with AD in Asian and white people.

METHODS

We included 34 studies with a total of 38 291 patients with AD and 55 538 controls of diverse races from four main databases. We used meta-analysis to obtain I -values and odds ratios of five genetic models in three SNPs. We carried out analysis of sensitivity, subgroup, publication bias and linkage disequilibrium test.

RESULTS

The forest plots showed the odds ratio value of the three SNPs was >1 in white individuals, but not Asian individuals, in their genetic model. The funnel plot was symmetrical, and the D'-value was 0.986 between rs744373 and rs7561528.

CONCLUSIONS

BIN1 rs744373, BIN1 rs7561528 and GAB2 rs2373115 are pathogenicity sites for AD in white people, and also rs7561528 belongs to a risk site in Asian people. The rs7561528 and rs744373 SNPs have strong linkage disequilibrium in Chinese people. In addition, apolipoprotein E ε4 status promotes them to result in the pathogenesis of AD. Geriatr Gerontol Int 2021; 21: 185-191.

摘要

目的

遗传因素在阿尔茨海默病(AD)发病机制中起着重要作用,尤其是易感基因的单核苷酸多态性(SNP),这是AD发病机制中的重要因素之一。BIN1基因的rs744373、rs7561528单核苷酸多态性以及GAB2基因的rs2373115单核苷酸多态性与亚洲人和白人的AD发病相关。

方法

我们从四个主要数据库中纳入了34项研究,共38291例AD患者和55538例不同种族的对照。我们采用荟萃分析来获取三个单核苷酸多态性在五种遗传模型中的I值和比值比。我们进行了敏感性分析、亚组分析、发表偏倚分析和连锁不平衡检验。

结果

森林图显示,在白人个体的遗传模型中,这三个单核苷酸多态性的比值比值大于1,但在亚洲个体中并非如此。漏斗图对称,rs744373和rs7561528之间的D'值为0.986。

结论

BIN1基因的rs744373、rs7561528以及GAB2基因的rs2373115是白人AD的致病位点,而rs7561528也是亚洲人的风险位点。在中国人群中,rs7561528和rs744373单核苷酸多态性存在强连锁不平衡。此外,载脂蛋白Eε4状态促使它们导致AD发病。《老年医学与老年病学国际杂志》2021年;21:185 - 191。

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