Both alleles of the M235T polymorphism of the angiotensinogen gene can be a risk factor for myocardial infarction

We have studied the role of three polymorphic genes of the renin-angiotensin system (RAS) as independent risk factors for myocardial infarction (MI) and their correlation with three of the major coronary risk factors: serum cholesterol (CH), hypertension (HT) and smoking (SM). A population of 392 men was genotyped for the M235T polymorphism of the angiotensinogen (AGT) gene. the insertion/deletion of the angiotensin-converting enzyme (ACE) and the all66c of the angiotensin-II type I receptor (ATR), by means of polymerase chain reaction (PCR) and restriction enzyme analysis. It was observed that the T allele frequency increased significantly in the MI with HT, CH, and SM subgroup (0.58 vs 0.31) (p < 0.01). In contrast, the M allele frequency was higher in the MI without HT, CH, and SM (0.69 vs 0.42) (p < 0.01). A strong association between the MM genotype and MI (p < 0.001, odds ratio = 4.29, confidence interval = 1.95-9.42) was found when age-matched MM control subjects were compared to MI individuals with none of the other known major coronary risk factors. Futhermore, subjects with the NIM genotype showed a significantly higher plasma renin activity (PRA) profile than those with the TT genotype (p < 0.001) It can be concluded that the M allele is an independent risk factor for MI and the T allele modified the risk when other major risk factors are present.