Genetic variation in the renin--angiotensin system, use of renin--angiotensin system inhibitors and the risk of myocardial infarction.
Maitland-van der Zee A-H., van Wieren-de Wijer DB., de Boer A., Kroon AA., de Leeuw PW., Schiffers P., Janssen RG., Psaty BM., van Duijn CM., Stricker BH., Klungel OH.
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.