Araújo Messias Antônio, Goulart Luiz Ricardo, Cordeiro Elisângela Rosa, Gatti Renata Ríspoli, Menezes Bruno Soares, Lourenço Clauber, Silva Heyder Diniz
Department of Internal Medicine, Medical School, Federal University of Uberlândia, Brazil.
Int J Cardiol. 2005 Aug 3;103(1):27-32. doi: 10.1016/j.ijcard.2004.07.009. Epub 2004 Dec 15.
Three-gene interactions among the genetic polymorphisms of the renin-angiotensin system (RAS) associated with acute myocardial infarction (AMI) have not been examined in a single population. We hypothesized that all types of gene-to-gene associations may occur in AMI, but that some will have a higher risk, depending on the gene frequencies.
Polymorphisms of the AGT (M235T), ACE (I/D) and AGTR1 (A1166C) genes in AMI patients and controls were analyzed using the polymerase chain reaction. Classic coronary risk factors were analyzed in all individuals.
Logistic regression analysis of these factors and the genetic polymorphisms demonstrated that smoking, family history of CAD, arterial hypertension and total cholesterol were the most significant contributors to AMI. The genotypic frequencies for all three genes alone were similar between the infarction and control groups, with no increased risk of developing AMI. Double homozygous combinations for normal alleles (MM of AGT, II of ACE and AA of AGTR1) had a lower risk of AMI (odds ratio<0.38), indicating a protective effect in these individuals. In genotypic combinations that included at least one unfavorable allele, the risk (odds ratio) of developing AMI was 2.92, 2.63 and 2.68 for AGT vs. ACE, AGT vs. ATR1 and ACE vs. AGTR1, respectively. The positive interaction among the three genes and the risk of AMI had an odds ratio of 3.78 with a 95% CI of 0.88-12.85.
The risk of developing AMI is higher whenever there are unfavorable alleles in gene-to-gene associations in the RAS.
肾素-血管紧张素系统（RAS）基因多态性之间的三基因相互作用与急性心肌梗死（AMI）的关系尚未在单一人群中进行研究。我们推测，AMI中可能会出现所有类型的基因-基因关联，但根据基因频率，某些关联会有更高的风险。
采用聚合酶链反应分析AMI患者和对照组中AGT（M235T）、ACE（I/D）和AGTR1（A1166C）基因的多态性。对所有个体分析经典的冠状动脉危险因素。
对这些因素和基因多态性进行逻辑回归分析表明，吸烟、CAD家族史、动脉高血压和总胆固醇是AMI的最主要促成因素。梗死组和对照组单独的所有三个基因的基因型频率相似，发生AMI的风险没有增加。正常等位基因的双纯合组合（AGT的MM、ACE的II和AGTR1的AA）发生AMI的风险较低（优势比<0.38），表明对这些个体有保护作用。在包含至少一个不利等位基因的基因型组合中，AGT与ACE、AGT与ATR1、ACE与AGTR1发生AMI的风险（优势比）分别为2.92、2.63和2.68。三个基因之间的正向相互作用与AMI风险的优势比为3.78，95%CI为0.88-12.85。
当RAS中基因-基因关联存在不利等位基因时，发生AMI的风险更高。
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