Genetic variation in the renin—angiotensin system,use of renin—angiotensin system inhibitors and the risk of myocardial infarction

Abstract

Introduction. This study investigated whether variation in the genes encoding for ACE, AGT and AGTR1 modifies the risk of myocardial infarction (MI) related to ACE inhibitors and AT II antagonists.

Methods. A nested case-control study among users of antihypertensive drugs, in whom the polymorphisms ACE-G4656C, ACE-T3892C, AGT-C235T and AGTR1-A1166C were genotyped.

Results. Among 613 cases and 3630 controls, the risk of MI was significantly lower among users of ACE inhibitors compared with that in users of other antihypertensives (adjusted OR, 0.78; 95% CI, 0.63—0.97). In patients using ACE inhibitors the largest risk reduction was found in patients carrying the ACE-4656-G allele (GC and GG genotypes) compared with patients carrying the CC genotype (OR, 0.68; 95% CI, 0.53—0.86 and OR, 1.26, 95% CI, 0.78—2.02, respectively). The synergy index for this interaction was statistically significant (SI, 0.58; 95% CI, 0.35—0.95). The risk of MI was reduced in those who were current users of ACE inhibitors those who had been prescribed dosages lower than the equivalent of 1 defined daily dose (DDD) and those having the AGTR1-1166AC or AA genotype compared with that in users of ACE inhibitors with the AGTR1-1166CC genotype (SI, 3.67; 95% CI,1.18—11.4). None of the polymorphisms modified the effectiveness of AT II antagonists regarding the risk of MI.

Conclusion. This study shows an interaction between the use of ACE inhibitors and ACE-G4656C polymorphism, and in low doses also with AGTR1-A1166C polymorphism, in the prevention of MI.

Keywords

ACE inhibitors ACE polymorphism angiotensin II type 1 receptor antagonists angiotensin II type 1 receptor polymorphism angiotensinogen polymorphism myocardial infarction pharmacogenetics

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