Zhang Yong, Tang Hai-Qin, Peng Wen-Jia, Zhang Bing-Bing, Liu Ming
Department of Cardiovascular Disease, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.
Chin Med J (Engl). 2015 May 20;128(10):1391-8. doi: 10.4103/0366-6999.156803.
Coronary heart disease (CHD) is a multifactorial disease and is thought to have a polygenic basis. Apolipoprotein E (APOE) gene is one such candidate with its common ε2/ε3/ε4 polymorphism in CHD. In recent years, numerous case-control studies have investigated the relationship of APOE polymorphism with CHD risk. However, the results are confusing.
To clarify this point, we undertook a meta-analysis based on 14 published studies including 5746 CHD cases and 19,120 controls. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for association using a random-effects or fixed-effects model using STATA version 10 (StataCorp LP, College Station, TX, USA).
Overall, the analysis showed that carriers of APOE ε2 allele decreased risk for CHD (ε2 allele vs. ε3 allele: OR = 0.82, 95% CI: 0.75-0.90, P < 0.001; ε2 carriers vs. ε3 carriers: OR = 0.81, 95% CI: 0.73-0.89, P < 0.001), compared with those carrying ε3 allele, especially in Caucasian population. However, those with ε4 allele had a significant increased risk for CHD (ε4 allele vs. ε3 allele: OR = 1.34, 95% CI: 1.15-1.57, P < 0.001), especially in Mongoloid population. Potential publication bias was observed in the genetic model of ε4 versus ε3, but the results might not be affected deeply by the publication bias. When we accounted for publication bias using the trim and fill method, the results were not materially alerted, suggesting the stability of our results.
Taken together, our meta-analysis supported a genetic association between APOE gene and CHD. ε4 increased the risk of CHD, whereas ε2 decreased the risk of CHD.
冠心病（CHD）是一种多因素疾病，被认为具有多基因基础。载脂蛋白E（APOE）基因就是这样一个候选基因，其常见的ε2/ε3/ε4多态性与冠心病有关。近年来，众多病例对照研究调查了APOE多态性与冠心病风险的关系。然而，结果却令人困惑。
为阐明这一点，我们基于14项已发表的研究进行了一项荟萃分析，这些研究包括5746例冠心病病例和19120例对照。使用随机效应或固定效应模型，利用STATA 10版本（美国德克萨斯州大学站市StataCorp LP公司）评估粗比值比（OR）及95%置信区间（CI）以确定关联性。
总体而言，分析表明，与携带ε3等位基因者相比，APOE ε2等位基因携带者患冠心病的风险降低（ε2等位基因与ε3等位基因：OR = 0.82，95% CI：0.75 - 0.90，P < 0.001；ε2携带者与ε3携带者：OR = 0.81，95% CI：0.73 - 0.89，P < 0.001），尤其是在白种人群中。然而，携带ε4等位基因者患冠心病的风险显著增加（ε4等位基因与ε3等位基因：OR = 1.34，95% CI：1.15 - 1.57，P < 0.001），尤其是在蒙古人种人群中。在ε4与ε3的遗传模型中观察到潜在的发表偏倚，但结果可能不会受到发表偏倚的严重影响。当我们使用修剪和填充法校正发表偏倚时，结果并未受到实质性影响，这表明我们结果的稳定性。
综上所述，我们的荟萃分析支持APOE基因与冠心病之间存在遗传关联。ε4增加冠心病风险，而ε2降低冠心病风险。
