Interaction between the G894TeNOS gene variant and calcium antagonists on the risk of myocardial infarction

Background: Nitric Oxide (NO) release might play a role in the effects of calcium antagonists on the prevention of MI. The G894T variant of the eNOS gene is associated with decreased NO release and may influence drug response. Objectives: To assess whether the association between use of dihydropyridines and risk of MI is modified by eNOS polymorphism. Methods: Nested case-control study among antihypertensive drug users. Cases were hospitalized for MI, controls who were not hospitalized for MI and were matched on age, gender, region and calendar date. Logistic regression analysis was used to calculate odds ratios (OR), synergy indices (SI), 95% confidence intervals (CIs) and to adjust for potential confounding factors. Results: Among 613 cases and 3627 controls, the risk of MI was increased among dihydropyridine users (OR 1.51; 95%CI 1.20-1.91) compared to users of other antihypertensive drugs (no calcium antagonists). Homozygous T allele carriers (12%) using dihyropyridines had a higher risk of MI than users of other antihypertensives (OR 2.82; 95%CI: 1.41-5.66), whereas homozygous G allele carriers did not have an increased risk (OR 1.25; 95%CI; 0.87-1.82). The interaction between current use of dihydropyridines and the TT genotype was statistically significant (SI 2.20; 95%CI: 1.05-4.60). Conclusions: Dihydropyridine use is associated with an increased risk of MI among homozygotes for the eNOS 894T allele, but not among homozygotes for the G allele.