Impact of NAD(P)H oxidase p22^phox gene polymorphism on vascular aging in Korean centenarian and nonagenarian

Background: Oxidative stress, the imbalance between production and removal of reactive oxygen species (ROS), is implicated in the process of cardiovascular aging. Membrane-associated NAD(P)H oxidase system is the most important source of ROS in vascular cells. p22^phox, a critical component of the NAD(P)H oxidase, has a polymorphic site on exon 4, associated with variable enzyme activity. The goal of this study is to investigate the effect of the p22^phox C242T polymorphism on cardiovascular aging. Methods: We investigated, in a cross-sectional study, the distribution of the p22^phox genotypes and its impact on vascular aging in elderly Korean subjects (N = 123, mean age ± SD: 97.0 ± 5.0). p22^phox C242T polymorphism was determined by PCR and restriction fragment length polymorphism analysis. The p22^phox genotype and allele frequencies were also compared with younger Korean subjects (N = 363, mean age ± SD: 49.0 ± 10.3). Results: No significant difference was identified in p22^phox genotype frequency according to the subject's age. However, the prevalence of CT + TT genotype was significantly less frequent in normotensive extremely elderly compared with younger subjects. Furthermore, the prevalence of the CT + TT genotype was significantly more frequent in hypertensive subjects (21.9%) than in the normotensive group (6.0%, P = 0.016) in extremely elderly subject. The association was more significant in systolic hypertension rather than diastolic hypertension. Mean systolic blood pressure and pulse pressure were also significantly higher in subjects with CT + TT genotype. In contrast, there was no significant association between p22^phox genotype and hypertension in younger-aged group. Conclusion: These results suggest an association between the p22^phox C242T polymorphism and vascular aging, which might be mediated by the increase of oxidative stress.