Lack of evidence for contribution of Glu298Asp (G894T) polymorphism of endothelial nitric oxide synthase gene to plasma nitric oxide levels

Introduction: Both positive and negative associations between a rare allele of 27-bp repeat polymorphism in intron 4 of endothelial nitric oxide synthase and plasma nitric oxide (NO) levels were previously reported, and further, these conflicting results were suggested to be partly accounted for smoking status of subjects. However, the genetic contribution of Glu298Asp (G894T) polymorphism to plasma NO levels with respect to smoking status has not been published. Methods: In a group of 411 healthy Korean subjects aged 19-81 years, the end product of NO (NO_x: nitrite plus nitrate) as an index of plasma NO levels was measured by the Griess method. The genotypes of G894T polymorphism were determined by the banding patterns on gel electrophoresis after restriction enzyme digestion. Results: Comparison of plasma NO_x levels revealed no significant differences across the genotypes and alleles of G894T polymorphism, which is independently of smoking status. However, significant differences in plasma NO_x levels between nonsmokers and smokers were observed (P=0.0040). Furthermore, only the common G allele was found to be responsible for these differences. Multiple regression analysis showed that the most independent contributing factor for plasma NO_x levels was smoking (P=0.0119) and followed by triglycerides (P=0.0384). Conclusions: Our results indicate no substantial effect of G894T polymorphism on the variance of plasma NO_x levels in healthy Korean population.