Subject & Aim. Endothelial nitric oxide synthase (eNOS) is one of the most important candidate genes in CAD. A functional polymorphism within eNOS gene is a 27？bp VNTR on its intron 4 which has been shown to be associated with various diseases. In this study we investigated eNOS VNTR polymorphism in addition to eNOS gene expression profile in patients with CAD. Material and Methods. The study comprised patients with angiographically confirmed CAD (CAD+) and individuals with normal coronary as CAD？. eNOS VNTR polymorphism frequencies were determined in both groups. In addition eNOS gene expression profile was examined using a quantitative real-time PCR. Results. We have found that aa genotype was significantly increasing the risk of CAD in our patients (aa versus ab + bb, , ; 95% CI: = 0.98 to 16.2). The differences in eNOS expression were not significant between patients and normal group; however in CAD+ patients eNOS expression was higher than the expression level of patients carrying other genotypes ( ). Conclusion. We have observed that eNOS gene polymorphism was associated with CAD in angiography-confirmed patients. However, the difference in eNOS gene expression was not statistically significant between patients and control which might be due to the contribution of other confounding factors which require further investigations. 1. Introduction Coronary artery disease (CAD) is one of the leading causes of death in the world. Familial aggregation of CAD indicates the contribution of genetic factors which might be involved in disease development. Genome-wide association studies have identified approximately 34 distinct loci in correlation with CAD [1]. Nitric oxide synthase (NOS) is one of the most important candidate genes in CAD. It is synthesizing NO in a catabolic reaction in presence of L-arginine [2]. The gene is located on chromosome 7q36 and is comprised of 3 isoforms in mammalian cells: neuronal (nNOS, type I), inducible (iNOS, type II), and endothelial (eNOS, type III). Most circulating NO is produced by these three isoforms [3, 4]. In all isoforms calmodulin domains become activated in the presence of resulting in enzyme activation [5]. Additionally, in the presence of stress, phosphorylations at Ser1177 of eNOS lead to Ca+2 sensitiveness which in turn results in enzyme activation [6, 7]. Vascular endothelial growth factor (VEGF) can also give rise to eNOS enzyme activation due to Ser/Thr kinase (Akt) function [8]. NO has essential role in vasodilatation via soluble guanylyl cyclase and cyclic GMP generation in smooth muscle cells [9–11].
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