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 (≥ 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 (≥ 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.