SOD3 and eNOS genotypes are associated with SOD activity and NOx

Abstract

Oxidative stress, characterized by increased reactive oxygen species production and/or decreased antioxidant enzyme activity, plays an important role in the pathogenesis of hypertension. The identification of molecular markers corresponding to the oxidative stress status of hypertension may assist in the antioxidant therapy of hypertension. In the present study, superoxide dismutase (SOD) and endothelial nitric oxide synthase (eNOS) were analyzed as markers of hypertension responding to oxidative stress. The plasma SOD activity and mononitrogen oxides (NOx) concentration were measured, and the SOD3 Ala58Thr and eNOS Glu298Asp polymorphisms were genotyped in hypertensive patients and normotensive controls. Further association experiments were replicated in an extended population, including 343 hypertensive patients and 290 controls. The results demonstrated that no statistically significant differences in the total SOD activity and NOx concentration were identified between the hypertensive patients and controls. However, the plasma SOD activity levels in the SOD3 Ala/Ala homozygote carriers (80.51±27.68 U/ml) were significantly lower compared with the Thr allele carriers (92.18±16.37 U/ml; P=0.031). In addition, the plasma NOx concentration in the eNOS Glu/Glu homozygote carriers (129.66±59.15 μmol/l) was significantly lower compared with the Asp allele carriers (169.84± 55.18 μmol/l; P=0.010). Notably, the altered SOD activity levels and NOx concentration were in concordance in 56.3% of the 80 participants. Therefore, the concordance of decreased SOD activity and NOx concentration, combined with genotypes of SOD3 Ala/Ala and/or eNOS Glu/Glu in hypertensive patients, may be useful in directing the antioxidant therapy of hypertension.