Interaction among 5,10 methylenetetrahydrofolate reductase, plasminogen activator inhibitor and endothelial nitric oxide synthase gene polymorphisms predicts the severity of coronary artery disease in Turkish patients.

ABSTRACT

BACKGROUND: Genetic factors play a role in the onset of coronary artery disease. The objective of our study is to evaluate the single locus and combined effects of three different genetic polymorphisms (methylenetetrahydrofolate reductase C677T polymorphism, plasminogen activator inhibitor 4G/5G polymorphism, and endothelial nitric oxide synthase 3-27 base pairs repeat polymorphism) on the presence and extent of coronary artery disease in patients with early-onset coronary artery disease. MATERIALS AND METHODS: DNA samples were obtained from 102 consecutive patients with symptoms resulting from early-onset coronary artery disease documented by coronary angiography. The severity of coronary artery disease in patients was stratified into three groups as one, two, or three-vessel coronary artery disease. The control group was selected from older subjects with a recent and negative cardiac work-up. Information on standard risk factors was collected. Multifactor dimensionality reduction analysis was performed to seek a model of coronary artery disease based on these three genetic polymorphisms. RESULTS: Single-locus effects of the three polymorphisms were not significantly related to the presence or severity of coronary artery disease. When gene-gene interactions were studied, however, the severity of disease was related to the frequency of high-risk alleles, yet advanced analysis did not detect a significant genetic model for coronary artery disease in these patients based on these three genetic polymorphisms. CONCLUSION: These three genetic polymorphisms are susceptibility loci and genotypes of these genes are neither necessary nor sufficient for the coronary artery disease to occur, but coexistence of high-risk alleles may increase the severity of coronary artery disease.