Ntzani Evangelia E, Rizos Evangelos C, Ioannidis John P A
Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
Am J Epidemiol. 2007 May 1;165(9):973-84. doi: 10.1093/aje/kwk085. Epub 2007 Feb 10.
Several genetic polymorphisms have been proposed to be associated with myocardial infarction (MI). The authors examined the evidence and biases underlying such associations using a case-study meta-analysis and an overview of large-scale data. In a meta-analysis of 27 studies addressing the association of the angiotensin type 1 receptor (AT1R)+1166A/C polymorphism with MI (10,180 cases, 17,129 controls), the *C allele conferred an increase in MI risk (odds ratio = 1.13 per allele, p = 0.005). However, there was large between-study heterogeneity; the largest study showed no effect, contradicting smaller studies; and studies with blinded genotyping showed no effect. The authors conducted an overview of meta-analyses of genetic associations for MI or coronary artery disease, including at least three studies and 3,000 subjects. In their latest meta-analysis, another 14 polymorphisms were found to have formally significant associations. If true, these associations would already explain 42% of the MI risk for Caucasian populations. Significant between-study heterogeneity was common. Across the 32 largest studies, only two found formally significant results (nine would be expected if each meta-analysis showed a true association). Even with large-scale evidence from meta-analyses, significant associations for MI may be subject to bias. Large-scale single studies and prospective consortia should be used for detecting and validating the genetic determinants of MI.
已有研究提出几种基因多态性与心肌梗死（MI）相关。作者通过病例研究的荟萃分析和大规模数据概述，对这些关联背后的证据和偏差进行了研究。在一项针对血管紧张素1型受体（AT1R）+1166A/C多态性与MI关联的27项研究的荟萃分析中（10180例病例，17129例对照），C等位基因使MI风险增加（每等位基因优势比=1.13，p=0.005）。然而，研究间存在很大的异质性；最大的研究显示无效应，这与较小规模的研究结果相矛盾；而采用盲法基因分型的研究也显示无效应。作者对MI或冠状动脉疾病的基因关联荟萃分析进行了概述，这些分析至少包括三项研究和3000名受试者。在他们最新的荟萃分析中，又发现另外14种多态性存在形式上显著的关联。如果这些关联是真实的，那么它们将已经能够解释白种人群中42%的MI风险。研究间显著的异质性很常见。在32项最大规模的研究中，只有两项得出了形式上显著的结果（如果每项荟萃分析都显示出真实关联，预计会有9项）。即使有来自荟萃分析的大规模证据，MI的显著关联仍可能存在偏差。大规模的单项研究和前瞻性联合研究应用于检测和验证MI的基因决定因素。
