P.049 The P22PHOX -930A/G Polymorphism of Nadph Oxidase: An Independent Genetic Determinant of Wave Reflections

Abstract

Introduction

Oxidative stress impairs wave reflections, which are independent markers and prognosticators of cardiovascular risk.The NADPH oxidase system maintains the redox state in the vessel wall. Recent studies have reported that the presence of allele G in the -930 polymorphic site of the p22^phox NADPH subunit is associated with increased enzyme activity, while the presence of allele A accounts for reduced activity. We investigated the relation between the -930^A/G polymorphism and wave reflections.

Methods

The study included 154 healthy individuals (102 males, mean age 40 years). The A-to-G substitution at position -930 in the p22^phox promoter was typed by BbvI digestion of specific polymerase chain reaction products amplified from genomic DNA. The AA, AG and GG genotypes were determined. Augmentation index (AIx) was measured as index of wave reflections, using a validated device (SphygmoCor).

Results

In our population, the prevalence of AA, AG and GG genotypes was 24%, 45.5% and 30.5% respectively. Multiple linear regression analysis revealed that after adjustment for age, systolic blood pressure, heart rate, gender, BMI and HDL cholesterol, subjects with GG genotype had significantly lower values of AIx by 5.89% compared to subjects with AA genotype (p<0.01), while subjects with AG genotype had significantly lower values of AIx by 4.77% compared to subjects with AA genotype (p<0.01).

Conclusion

Our findings suggest that the -930^A/G polymorphism of the p22^phox promoter of NADPH oxidase is an independent determinant of wave reflections in healthy individuals. Presence of the G allele is associated with lower values of AIx.