Association between the Glu298Asp and 4b/4a polymorphisms of endothelial nitric oxide synthase and coronary slow flow in the North Indian population

RATIONALE: Genetic variants in endothelial nitric oxide synthase gene (NOS3) leading to endothelial dysfunction may be predispose to the coronary slow-flow phenomenon (CSFP). METHODS AND RESULTS: In this study, we examined the relationship between Glu298Asp (894G/T) and 4b/4a polymorphisms of NOS3 and CSFP. A total of 27 patients with CSFP but otherwise normal coronary arteries (mean age 50.4±8.2 years) and 200 controls with a normal coronary angiogram (mean age 53.1±8.6 years) were screened for Glu298Asp and 4b/4a polymorphisms by restriction fragment length polymorphism and PCR, respectively. Nitric oxide levels were determined using Griess' enzymatic method for an association with the polymorphisms. The genotype distribution of the Glu298Asp polymorphism differed significantly between the CSFP patients and controls (P=0.004). The dominant genetic model showed that GT+TT was significantly prevalent in patients in comparison with controls (P=0.014) and the T allele was significantly prevalent in patients (P=0.002). The genetic distribution of 4b/4a differed significantly for the heterozygous genotype ba (P=0.047). The overdominant genetic model re-established that the ba genotype was significantly prevalent in patients (P=0.044). Nitric oxide level was higher in patients than in controls, the values being 144.51±43.25 and 129.64±29.47 μmol/l, respectively (P>0.05). The genotypes of Glu298Asp showed a trend of association with nitric oxide levels, which decreased linearly in the order of GG, GT, and TT (P>0.05). CONCLUSION: The Glu298Asp polymorphism of NOS3 associates with CSFP.