The effect of p22(phox) -930A/G, A640G and C242T polymorphisms of NADPH oxidase on peripheral and central pressures in healthy, normotensive individuals.

The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase produces superoxide, thus regulating redox state in the vessel wall. Three single-nucleotide polymorphisms (SNPs; -930A/G, A640G and C242T) of the p22(phox) subunit have been associated with hypertension; however, their role in peripheral and central pressures in normotensive individuals has not been addressed. A total of 210 healthy, normotensive individuals were studied. Genotypes for the -930A/G, A640G and C242T polymorphisms were determined by polymerase chain reaction. Peripheral pressures were measured by mercury sphygmomanometer and aortic pressures by a validated device using applanation tonometry. Both peripheral and central pressures differed across -930A/G genotypes. G allele carriers showed higher levels of peripheral systolic blood pressure (PSBP; AA: 113+/-12, GG/AG: 119+/-12 mm Hg; P<0.01) and peripheral diastolic blood pressure (AA: 70+/-9, GG/AG: 73+/-10 mm Hg; P<0.05). Regarding central pressures, AA homozygotes had lower central systolic blood pressure (CSBP; AA: 103+/-12, GG/AG: 108+/-12 mm Hg; P<0.01) and central diastolic blood pressure (AA: 71+/-9, GG/AG: 74+/-10 mm Hg; P<0.05). In multiple linear regression analysis, presence of the G allele (AG or GG) independently predicted CSBP. Blood pressure levels did not differ across A640G and C242T genotypes. The -930A/G polymorphism of p22(phox) is a determinant of peripheral and central pressures in normotensive individuals. The G allele is associated with higher blood pressure in the brachial artery, as well as in the aorta. These findings further elucidate the role of this polymorphism in the regulation of blood pressure. In contrast, the A640G and C242T SNPs do not influence peripheral and central pressures in normotensives.