摘要：

目的 探讨中国人群载脂蛋白E（ApoE）基因多态性与迟发性阿尔茨海默病的关系。方法 以载脂蛋白E 基因（ApoE）、迟发性阿尔茨海默病（late onset Alzheimer's disease）、基因多态性（polymorphism）、China 和Chinese 等中英文词组，检索美国国立医学图书馆生物医学信息检索系统、荷兰医学文摘、EBSCO-CINAHL、Cochrane 图书馆，以及中国生物医学文献数据库、中国知网中国知识基础设施工程、万方数据库等近20年发表的关于中国人群ApoE 基因多态性与迟发性阿尔茨海默病关系的病例对照研究，采用Newcastle-Ottawa 量表（NOS）进行文献质量评价，RevMan 5.0 统计软件进行Meta 分析。结果 共获得249 篇文献，经剔除重复和不符合纳入标准者并补充相关文献，最终纳入13 篇高质量临床研究（NOS 评分≥ 5 分），共3372 例受试者（迟发性阿尔茨海默病患者1360 例、对照者2012 例）。Meta 分析显示：携带ApoEε4 等位基因者发生迟发性阿尔茨海默病的风险高于携带ApoEε3 等位基因者（OR = 3.710，95%CI：2.960 ~ 4.640；P = 0.000）；表现为ApoEε3/ε4（OR = 3.160，95%CI：2.390 ~ 4.180；P = 0.000）、ApoE ε 2/ε 4（OR = 3.410，95%CI：2.160 ~ 5.380；P = 0.000）和ApoE ε 4/ε 4（OR = 16.400，95%CI：8.200 ~ 32.810；P = 0.000）基因型者发生迟发性阿尔茨海默病的风险高于ApoEε3/ε3 基因型者。结论 携带ApoEε4 等位基因，以及ApoEε3/ε4、ApoEε2/ε4 和ApoEε4/ε4 基因型是中国人群发生迟发性阿尔茨海默病危险因素。

关键词: 载脂蛋白E 类, 基因, 阿尔茨海默病, Meta分析, 中国

Abstract:

Objective To systematically review the correlation between genetic polymorphism of apolipoprotein E (ApoE) and late onset Alzheimer's disease (LOAD) in Chinese population. Methods Taking "ApoE, late onset Alzheimer's disease, polymorphism, China and Chinese" as retrieval words, databases of PubMed, EMBASE/SCOPUS, EBSCO-CINAHL, Cochrane Library, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang Data were retrieved with computer for collecting case-control studies about the correlation between genetic polymorphism of ApoE and LOAD in Chinese population in recent 20 years. Newcastle-Ottawa Scale (NOS) was used for methodological quality assessment. Meta-analysis was conducted by using RevMan 5.0 software. Results  There were a total of 249 records through preliminary searching. After eliminating 113 duplicate ones and 124 articles which did not meet the inclusion criteria and adding one article by searching the references of 27 screened articles, 13 high-quality clinical trials were finally selected (NOS score ≥ 5). A total of 3372 subjects (1360 LOAD patients and 2012 controls) were included. Meta-analysis showed that the LOAD risk in population with allele ApoEε4 was significantly higher than those with allele ApoEε3 (OR = 3.710, 95%CI:2.960-4.640; P = 0.000), while had no statistical difference from those with allele ApoEε 2. Meta-analysis also showed that the LOAD risk in those with genotype ApoEε3/ε4 (OR = 3.160, 95%CI: 2.390-4.180; P = 0.000), genotype ApoE ε 2/ε 4 (OR = 3.410, 95% CI: 2.160-5.380; P = 0.000), genotype ApoE ε 4/ε 4 (OR = 16.400, 95% CI: 8.200-32.810; P = 0.000) was significantly higher than those with genotype ApoE ε 3/ε 3, while had no statistical differences from those with genotype ApoE ε 2/ε 3 and genotype ApoE ε 2/ε 2. Conclusions The evidences indicate that ApoEε4 allele and ApoE genotype ε3/ε4, ε2/ε4 and ε4/ε4 are high risk factors for LOAD in Chinese population.

Key words: Apolipoproteins E, Genes, Alzheimer disease, Meta-analysis, China