Relation of the Glu298Asp polymorphism of the nitric oxide synthase gene to hypertension and serum cholesterol in Japanese workers.

Objective: To assess whether the Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene possibly mediates the relation of blood pressure and serum cholesterol.

Method: Regular health examination in 2003 of 1,694 Japanese workers from the Shimane Prefecture, Japan.

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 stress), the odds ratio (OR) of hypertension associated with high (> or = 220 mg/dl or under treatment) total cholesterol was 2.08 (95% Confidence Interval (CI) 1.02-4.24) among carriers of the eNOS 298Asp allele versus 1.18 (95% CI 0.89-1.55, p for interaction=0.50) among non-carriers. Similarly, the ORs of hypertension associated with counseling-need (120-139 mg/dl) and high (> or = 140 mg/dl) levels of LDL cholesterol among carriers of the eNOS 298Asp allele were significantly higher than those among non-carriers, at 2.65 (95% CI 1.16-6.01) versus 1.03 (95% CI 0.77-1.39, p for interaction=0.01), and 2.80 (95% CI 1.33-5.89) versus 0.95 (95% CI 0.71-1.26, p for interaction=0.04), respectively.

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