P7.13 THE P22PHOX -640A/G POLYMORPHISM OF NADPH OXIDASE ADVERSELY AFFECTS ENDOTHELIN LEVELS BUT NOT PERIPHERAL AND CENTRAL PRESSURES IN HEALTHY, YOUNG, NORMOTENSIVE INDIVIDUALS

Abstract

Purpose: The NADPH oxidase system produces superoxide in the vessel wall and its -640A/G polymorphism is associated with coronary artery disease incidence in young individuals. We investigated the role of this polymorphism on peripheral/aortic pressures (PP, AoP), and endothelin-1 (ET-1) levels, in young normotensive individuals. Methods: 153 healthy normotensives were studied (95 males, age 41 years). The -640A/G polymorphism in the p22phox promoter was typed by DraIII digestion of specific polymerase chain reaction products amplified from genomic DNA. The AA, AG and GG genotypes were determined. PP were measured by a sphygmomanometer; AoPs were measured using a validated device. ET-1 levels were determined by ELISA. Comparisons were performed using the ANOVA for multiple comparisons followed by Bonferonni correction. Results: The prevalence of AA, AG and GG genotypes was 26.8%, 49% and 24.2%. Compared to AG subjects, AA and GG subjects had significantly higher levels of ET-1 (AG: 1.69±3.50 vs AA: 4.35±6.62 vs GG: 2.70±5.28pg/mL, p<0.05). However, neither PPs nor AoPs differ; systolic PP (AG: 113.8±13.2 vs AA: 116.9±11.5 vs GG: 116.4±16.1 mmHg, p=NS), diastolic PP (AG: 70.5±11.2 vs AA: 71.7±9.2 vs GG: 71.1±12.4 mmHg, p=NS), systolic AoP (AG: 103.9±12.8 vs AA: 105.1±11.3 vs GG: 105.9±16 mmHg, p=NS), diastolic AoP (AG: 71.5±11.2 vs AA: 72.7±9.3 vs GG: 72.2±12.6 mmHg, p=NS). Conclusion: The -640A/G polymorphism of the p22phox subunit of NADPH oxidase is associated with levels of ET-1, but neither with PP nor with AoP in young, normotensive individuals. Heterozygosity is associated with lower ET-1 levels.