CYBA C242T gene polymorphism and flow-mediated vasodilation in a population of young adults: the Cardiovascular Risk in Young Finns Study

OBJECTIVE: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a major source of the superoxide anion that contributes to decreased nitric oxide bioavailability in the vasculature. The C242T polymorphism of the CYBA gene that encodes p22phox, a component of NADPH oxidase, has been found to modulate superoxide production. We examined the relationship of the C242T polymorphism with endothelial-dependent brachial artery flow-mediated vasodilatation (FMD) in a population-based sample of young healthy adults. METHODS: FMD, defined as the increased percentage in brachial artery diameter after reactive hyperemia, was assessed by ultrasound and the C242T polymorphism using a 5' nuclease assay in 2058 subjects aged 24-39 years. RESULTS: The mean values of brachial artery FMD were 8.0 +/- 4.4% in all study subjects (n = 2058), and 7.8 +/- 4.4, 8.2 +/- 4.5, and 8.7 +/- 4.5% in subjects with the CC (n = 1362), CT (n = 616), and TT (n = 80) genotypes of the C242T CYBA polymorphism, respectively (P = 0.02 for trend). The association remained significant (P = 0.019) in multivariate analyses adjusted for age, sex, obesity indices, smoking habits, blood pressure, serum glucose, lipids, and C-reactive protein. The relationship between FMD and the C242T polymorphism was stronger (P = 0.004) in overweight subjects (body mass index > or = 25 kg/m, n = 895) and ever-smokers (P = 0.008, n = 1082), whereas no relationship was found in normal-weight subjects and non-smokers (P = 0.824 and P = 0.438, respectively). CONCLUSION: The C242T polymorphism of the CYBA gene seems to be related to endothelial function in a population-based sample of young healthy adults. Overweight and smoking status may modify this genetic effect.