Role of endothelial nitric oxide synthase Glu298Asp gene variant in modulating blood pressure through a relationship with lipid levels

Objective: To clarify the causal relationship between plasma cholesterol and blood pressure, the effects of the Glu298Asp polymorphism of the endothelial NO synthase (eNOS) gene on the association between blood pressure and serum lipid levels were examined.

Methods: The data among 1,694 Japanese workers in Shimane Prefecture, Japan, were obtained at regular health examination in 2003, and we tested for an association of the eNOS Glu298Asp polymorphism and plasma levels of lipids and lipoproteins in the determination of hypertension.

Results: The frequencies of the Glu/Glu, Glu/Asp, and Asp/Asp genotypes were 85.9%, 13.4%, and 0.7%, respectively. After adjustment for age, sex, BMI, and lifestyle (drinking, smoking, exercise, and the degree of stress exposure), logistic regression analysis showed that, in subjects with the eNOS 298Asp allele, the odds ratio (OR) of hypertension associated with high (³220 mg/dl or under treatment) level of total cholesterol was significantly higher (p=0.043), at 2.08 (95% CI, 1.02-4.24). Similarly, the ORs of hypertension associated with counseling-need (120-139 mg/dl) and high (³140 mg/dl)levels of LDL cholesterol were significantly higher, at 2.65 (95% CI, 1.16-6.01, p=0.02) and 2.80 (95% CI, 1.33-5.89, p=0.007), respectively.

Conclusion: These results indicate that the eNOS 298Asp allele, which is weakly associated with hypertension, may increase the risk of hypertension associated with serum lipid profiles.