Association Patterns of Endothelial Nitric Oxide Synthase Gene (NOS3) Variant Glu298Asp with Blood Pressure and Serum Lipid Levels in Subjects with Coronary Artery Disease from Pakistan

Nitric oxide is an important antiatherosclerotic agent. The main determinant of nitric oxide levels is enzyme nitric oxide synthase encoded by the NOS3 gene, the common variants in this gene may be responsible for variations in plasma enzyme levels. The association of NOS3 variants with coronary artery disease (CAD) varies in different ethnicities. The current study aimed to determine the association of NOS3 Glu298Asp (rs1799983) with CAD and blood lipid levels in Pakistani subjects. Six hundred thirty-six samples (412 cases, 224 controls) were genotyped by TaqMan allelic discrimination assay and serum total cholesterol, and High Density Lipoprotein cholesterol (HDL-C)/Low Density Lipoprotein cholesterol (LDL-C) and triglycerides were measured. The genotype frequency was Glu/Glu = 64.6%, Glu/Asp = 30.1%, and Asp/Asp = 5.3% in cases, and Glu/Glu = 68.8%, Glu/Asp = 26.7%, and Asp/Asp = 4.5% in controls. The Asp298 (T) frequency was not significantly higher in cases than controls (20.4% vs 17.9%, P = 0.28) and risk allele was not associated with CAD (OR 1.15 (0.86–1.54), P = 0.33) and the tested lipid traits but had a strong association with blood pressure (for systolic and diastolic P = 1.9×10−–56 and 4×10−–40, respectively). In conclusion, although Glu298Asp did not show association with CAD and lipid profile in the studied cohort, it may exert its effect through blood pressure; however, the mechanism of this effect needs to be explored in the future.