The contribution of NOS3 variants to coronary artery disease: A combined genetic epidemiology and computational biochemistry perspective.

Cardiovascular diseases, particularly coronary artery disease (CAD) and myocardial infarction, are the leading cause of death among people worldwide. CAD is exceedingly complex in its interplay of environment and genetics, with numerous genetic loci contributing to its heritability. Here, we aim at looking into the effects of the NOS3 c.894G>T and 27-bp VNTR polymorphisms on susceptibility to CAD in a population of Turkish Cypriots, at seeing whether these effects correlate with plasma lipid levels and at predicting the functional consequences of each polymorphism tested. A total of 50 subjects with CAD and 100 otherwise healthy subjects were included in the present case-control study. Genomic DNA was extracted from peripheral blood samples, and the two NOS3 polymorphisms were determined by restriction endonuclease analysis of PCR amplicons. Complementary methods of statistical analysis and computational modeling were employed accordingly to achieve the aims above. Our findings show that the 27-bp VNTR polymorphic locus, but not the c.894G>T polymorphic locus, is associated with CAD and that it may regulate NOS3 pre-mRNA splicing in a length-dependent manner. Overall, along with additional, yet-to-be ascertained susceptibility markers the 27-bp VNTR 4a/4b marker may be employed in risk stratification in community-level screening for CAD among Turkish Cypriots.