Influence of Klotho Genotypes on Plasma NO(x) Levels in South Indian Population

Introduction: Despite experimental evidences of the influence of the aging suppressor gene Klotho, on the modulation of endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production, the contribution of its variants to the phenotypic variance of plasma nitrite and nitrate (NO(x)) has not been addressed to date. In the present study, we aimed to determine the influence of two exonic variants, KL-VS and C1818T of Klotho, on circulating NO(x) levels in South Indian population.

Materials And Methods: We genotyped the two Klotho KL-VS and C1818T variants in 429 healthy South Indians and measured their plasma NO(x) concentrations by the Griess method.

Results: Genotype frequencies were compared in subjects with low and high NO(x) levels. An age-specific association of the Klotho C1818T variant was found with plasma NO(x) levels in subjects aged >40 years (p=0.027); the CC homozygotes were more prevalent in the low compared to the high plasma NO(x) group. However, the variant was not associated with plasma NO(x) levels in subjects aged≤40 years (p=0.799). The KL-VS variant did not have any influence on plasma NO(x) status (p=0.260).

Conclusions: Our results suggest that the effect of Klotho C1818T variant on levels of plasma NO(x) becomes pronounced with age probably implying the adaptive capability of Klotho alleles to meet the age-related increasing physiological load.