Genetic polymorphisms and interactions associated with myocardial infarction.

摘要

Myocardial infarction (MI) is characterized by arterial occlusion and thrombosis. Genes involved in vasoconstriction, smooth muscle cell proliferation, fibrinolysis, and oxidative stress may contribute to MI. Polymorphisms in angiotensin I converting enzyme (ACE), angiotensin II type I receptor (AT1R), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (TPA), and endothelial cell nitric oxide synthase (ecNOS) were examined for association with MI in a study of 245 incident MI cases and 202 controls with no history of thrombosis. Objectives were to estimate marginal effects of gene polymorphisms, to assess gene-gene and gene-environment interactions, and to compare case-control versus case-only genetic interaction results. AT1R transversion from adenine (A) to cytosine (C) at nucleotide position 1166 was associated with MI. Threefold association between AT1R CC genotype and MI observed in Whites (odds ratio (OR) = 3.10) was attenuated when Blacks were included (race-adjusted OR = 2.64). The C allele is rare in Blacks. After controlling for self-reported race, there was no association among controls between genotypes and potential confounding factors including age, gender, education, income, body mass index, and comorbid medical conditions. Interactions were assessed for genes in the renin-angiotensin system (ACE, AT1R), the fibrinolytic system (TPA, PAI-1), and endothelial cell nitric oxide synthase (ecNOS). Gene-gene interactions within each molecular pathway were not significant. We assessed interaction of genetic effects by demographic (age, race, gender) and medical (hypertension, diabetes, obesity, smoking) factors. Gender interaction with PAI-1 genotype was significant in case-control (p = 0.03) and case-only analyses (p = 0.003), though there was no overall association between PAI-1 genotype and MI. We observed no effect modification by other medical or demographic factors. Further studies of AT1R and PAI-1 genes may yield insight into the complex etiology of MI.