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.
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.
Authors: Roberto Schreiber; Maria C Ferreira-Sae; Juliana A Ronchi; José A Pio-Magalhães; José A Cipolli; José R Matos-Souza; José G Mill; Aníbal E Vercesi; José E Krieger; Kleber G Franchini; Alexandre C Pereira; Wilson Nadruz Junior Journal: BMC Med Genet Date: 2011-08-31 Impact factor: 2.103
Authors: Roberto Schreiber; Vera Regina Bellinazzi; Andrei C Sposito; José G Mill; José E Krieger; Alexandre C Pereira; Wilson Nadruz Journal: PLoS One Date: 2013-12-05 Impact factor: 3.240