Endothelial Nitric Oxide Synthase Intron 4a/b Gene Polymorphism and Ischemic Heart Disease among Smokers: A Pilot Study

Abstract

IHD is one of the most common causes of morbidity and mortality worldwide. It is responsible for 47% of deaths in Egypt. Ischemia of the myocardium emerges from decreased oxygen supply in relation to demands. Currently, atherosclerosis is the basis of IHD. Inflammation has a major role in the pathogenesis of atherosclerosis. Clinically, IHD presents either by ACS or CCS. It may be asymptomatic, may manifest by stable or unstable angina, acute myocardial infarction or sudden death. Diagnosis of IHD is confirmed by ECG, elevated cardiac markers and imaging techniques. NO is a soluble gas with a very short half -life that is synthesized and released in a continuous fashion in our body and it is considered the most important molecule produced by the vascular endothelium. It has many activities that play a major role in vascular homeostasis including vascular relaxation, inhibition of platelet and leukocyte adhesion to the vascular wall and inhibition of proliferation of smooth muscles. It is also protective against atherosclerotic changes. Decreased NO activity facilitates vascular inflammation and formation of foam cells. Synthesis of NO is mediated by the action of an enzyme NOS. It acts on Arginine to produce Citrulline and NO. NOS enzyme has three isoforms; iNOS, nNOS and eNOS. Endothelial NOS is mainly expressed in the vascular endothelium, also detected in platelets and cardiac muscles. Many environmental factors may affect eNOS activity like cigarette smoking and aging. NOS3 gene encodes the protein eNOS and is located on the long arm of chromosome 7 and it is thought to play an important role the in the pathogenesis of IHD. Individual variations in NO production are explained by polymorphism on the genetic level. The polymorphism of interest in this study is a 27 base pair (bp) repeat in intron 4. We conducted this study to assess the association between intron 4a/b gene polymorphism and IHD among smokers; it was a pilot study that included 60 subjects in two groups. The cases group included 3