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Background: 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., Methods: 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., Results: 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., Conclusions: The risk of developing AMI is higher whenever there are unfavorable alleles in gene-to-gene associations in the RAS.

Objective: To study the effect of the angiotensinogen gene M235T polymorphism on coronary artery disease and its severity in patients with and without acute myocardial infarction., Methods: A cross sectional study was carried out with 305 Caucasians who were divided into two groups. One group with 201 patients with coronary artery disease proven by coronary angiography (obstructive lesion > 50%) was further divided into two subgroups; 110 patients with acute myocardial infarction and 91 without it. The control group consisted of 104 individuals with normal coronary arteries. Three angiographic criteria were evaluated to determine severity of the coronary artery disease: number of diseased vessels, morphology of the atherosclerosis plaque and jeopardy score. Risk factors were also analyzed. Gene polymorphism was evaluated by the polymerase chain reaction followed by restriction endonuclease digestion., Results: The angiotensinogen gene TT, MT and MM genotypic frequencies were neither statistically different between coronary artery disease patients and controls (chi-square = 0.123; p = 0.939) nor between the acute myocardial infarction subgroup (chi-square = 2.171; p = 0.338). The coronary artery disease and acute myocardial infarction risk analyzed between TT vs. MM, MT vs. MM and TT+MT vs. MM genotypes were not significant. The severity of atherosclerotic disease analysis within the group of patients with coronary artery disease showed no correlation with the genotypes. Similar results were found between groups with and without acute myocardial infarction., Conclusions: No association was found between the angiotensinogen gene M235T polymorphism and coronary artery disease, neither with its severity nor with acute myocardial infarction.