载脂蛋白 E ε4 纯合子对阿尔茨海默病的遗传抗性：系统评价。
Genetic resilience to Alzheimer's disease in APOE ε4 homozygotes: A systematic review.
机构信息
Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Department of Genomic Medicine, Royal Melbourne Hospital, Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia.
Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
出版信息
Alzheimers Dement. 2019 Dec;15(12):1612-1623. doi: 10.1016/j.jalz.2019.05.011. Epub 2019 Sep 7.
INTRODUCTION
Individuals with homozygosity for the apolipoprotein E (APOE) ε4 allele are in the highest risk category for late-onset Alzheimer's disease (LOAD). However, some individuals in this category do not develop LOAD beyond the age of 75 years, despite being at elevated genetic risk. These "resilient" individuals may carry protective genetic factors.
METHODS
This study aimed to systematically review any previous studies that involved resilient APOE ε4 homozygotes and to identify possible modifying or protective genetic factors.
RESULTS
Fifteen studies met our inclusion criteria and reported genetic factors contributing to reduced risk. We found that only two single nucleotide polymorphisms, CASP7 rs10553596 and SERPINA3 rs4934-A/A, had strong evidence.
DISCUSSION
We found a paucity of studies adequately designed to discover protective genetic factors against LOAD. Many studies combined APOE ε4 homozygotes and heterozygotes together because of small sample sizes and used control populations too young to be clearly defined as controls for LOAD.
简介
载脂蛋白 E（APOE）ε4 等位基因纯合的个体处于晚发性阿尔茨海默病（LOAD）的最高风险类别。然而，尽管遗传风险较高，该类别中的一些人在 75 岁以上不会发展为 LOAD。这些“有韧性”的个体可能携带保护性遗传因素。
方法
本研究旨在系统回顾任何以前涉及有韧性的 APOE ε4 纯合子的研究，并确定可能的修饰或保护性遗传因素。
结果
符合纳入标准并报告有助于降低风险的遗传因素的研究有十五项。我们发现只有两个单核苷酸多态性，CASP7 rs10553596 和 SERPINA3 rs4934-A/A，具有强有力的证据。
讨论
我们发现，设计用于发现 LOAD 保护性遗传因素的研究很少。由于样本量小，许多研究将 APOE ε4 纯合子和杂合子合并在一起，并使用年龄太小而无法明确界定为 LOAD 对照的对照人群。
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