Endocrine Abstracts

Increased superoxide(SO) production reduces nitric oxide(NO) bioactivity and increases oxidative stress contributing to endothelial dysfunction in vascular disease. The gene coding for p22phox, a critical component of the NADH/NAD(P)H oxidase enzyme system which produces vascular SO, is CYBA. Among the allelic polymorphisms reported in CYBA is C242T which is associated with progression of coronary atherosclerosis. Radial applanation tonometry with pulse waveform analysis (PWA) can be utilized to document vascular disease in discrete groups and also changes in NO bioactivity. We examined the relationship between the CYBA C242T polymorphism and this non-invasive vascular intermediate phenotype.
Ethical approval was obtained. 37 patients with angiographically documented coronary artery disease (CAD) were recruited. Genotypes were determined with polymerase chain reaction and restriction digestion. Radial artery pressure waveforms were recorded using a calibrated tonometer and Windkessel based diastolic pressure decay analysis then used to generate large(C1) and small(C2) artery compliance values. Differences between genotype groups were analysed using unequal variance unpaired Student's t tests.
The distribution of the genotypes and frequency of the alleles of the C242T polymorphism were in Hardy-Weinberg equilibrium CC n=17 (46%), CT n=16 (43%), TT n=4 (11%). There was no significant difference in age or diastolic blood pressure between genotype groups. The presence of the T allele (ie CT + TT vs CC) was associated with increased systolic blood pressure (140.42 +/- 20.38 mmHg vs 122.87 +/- 16.47 mmHg ;95% CI for the difference in the mean 4.66, 30.45; p<0.01) and lower large (12.46 +/- 4.36 ml/mmHg x 10 vs 17.15 +/- 5.31ml/mmHg x 10 ;95% CI 1.20, 8.18; p=0.01) and small artery compliance values (3.07 +/- 1.36 ml/mmHg x 100 vs 4.71 +/- 2.79 ml/mmHg x 100 ;95% CI 0.00, 3.28; p=0.05).
PWA is a non-invasive, quantitative vascular phenotype which can be used to assess the effects of genotype on vascular compliance.