载脂蛋白 E 基因型与阿尔茨海默病的种族相关性：系统评价和荟萃分析。

Race-Related Association between APOE Genotype and Alzheimer's Disease: A Systematic Review and Meta-Analysis.

机构信息

Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China.

出版信息

J Alzheimers Dis. 2021;83(2):897-906. doi: 10.3233/JAD-210549.

DOI:10.3233/JAD-210549

PMID:34334408

Abstract

BACKGROUND

The global race-dependent association of Alzheimer's disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations.

OBJECTIVE

This study aims to determine how race and APOE genotype affect the risks for AD.

METHODS

We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes.

RESULTS

The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOEɛ4 was a risk factor for AD, whereas APOEɛ2 protected against it. The effects of APOEɛ4 and ɛ2 on AD risk were distinct in various races, and they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOEɛ4/ɛ4 and lower frequency of APOEɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races.

CONCLUSION

Our meta-analysis suggests that the association of APOE genotypes and AD differ among races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.

摘要

背景

阿尔茨海默病（AD）与载脂蛋白 E（APOE）基因型的全球种族依赖性关联尚不清楚。APOE 的跨种族分析可以阐明遗传在不同人群 AD 风险中的作用。

目的

本研究旨在确定种族和 APOE 基因型如何影响 AD 的风险。

方法

我们从 1993 年到 2020 年 8 月 25 日，在 PubMed、Embase、Web of Science 和 Cochrane Library 中进行了系统检索。共确定了 10395 份报告，其中 133 份符合分析条件，纳入了 77402 名参与者的数据。这些研究包含 AD 临床诊断和 APOE 基因型数据。在病例对照分析中，对不同种族和 APOE 基因型的同质数据集进行了汇总。为不同种族的人群计算了发生 AD 的比值比（OR）和 95%置信区间（CI）。

结果

不同种族人群的 APOE 基因型和等位基因比例不同。结果表明，APOEɛ4 是 AD 的危险因素，而 APOEɛ2 则对其有保护作用。APOEɛ4 和 ɛ2 对 AD 风险的影响在不同种族之间存在差异，并且在黑人中明显减弱。亚组分析发现，在合并组和不同种族中，早发性 AD 比晚发性 AD 中 APOEɛ4/ɛ4 的频率更高，APOEɛ3/ɛ3 的频率更低。