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.