Role of eNOS genetic variants on ischaemic heart disease susceptibility and acute coronary syndrome presentation

Abstract Aims IHD is determined by inadequate coronary blood supply to myocardium and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Results validation on larger cohorts and new population is needed. The aim of the study is to evaluate the association among the allelic variants of eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility, and its clinical presentation. Methods A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD); G2, coronary microvascular dysfunction (CMD); G3, control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG, and TT of rs1799983 for NOS3 gene, encoding for eNOS has been performed. Results rs1799983_GT is significantly more expressed by ischaemic groups (G1 and G2) compared with G3. The TT variant is significantly more expressed by G1 group, compared with G2 group. Among ischaemic patients, GT is significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentation. At multivariate analysis, the allelic variant GT may represent an independent predictor of IHD and ACS presentation. Conclusions The SNP rs1799983_GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently from cardiovascular risk factors. These results may be useful for the prediction of IHD development, in particular with acute clinical manifestation. It may allow the early identification of patients at high risk to develop IHD with an ACS, promoting a genetic-based prevention strategy against IHD.