Endocrine Abstracts (2006) 11 P305

A gene gene interaction of single nucleotide polymorphisms within two oxidative stress genes affects arterial compliance in patients with coronary artery disease

RS Drummond1, HHC Koh-Tan1, NJR Brain1, JD McClure1, LM Cherry1, AJB Kirk2, N Sattar1, JMC Connell1 & AF Dominiczak1


1BHF Glasgow Cardiovascular Research Centre, University Of Glasgow, Western Infirmary Glasgow, Glasgow, United Kingdom; 2Department of Cardiothoric Surgery, Western Infirmary, Glasgow, United Kingdom.


We hypothesised that SNPs within oxidative stress genes influence vascular compliance in patients with coronary artery disease.

A SNP within the gene encoding the eNOS (NOS3) which encodes a Glu298→Asp amino acid substitution has been associated with cardiovascular disorders in which NO bioactivity is impaired. The gene coding for p22phox, a critical component of the NADH/NAD(P)H oxidase enzyme system, a major source of vascular SO, is CYBA. An allelic polymorphisms of CYBA, C242T, is associated with progression of coronary atherosclerosis. Consistent characteristic changes in the pulse pressure waveshape are associated with ageing, risk factors for cardiovascular disease and impaired NO bioactivity. Radial applanation tonometry with pulse waveform analysis can be utilized to quantify arterial compliance and dynamic changes in NO bioactivity.

Local ethical committee approval was obtained for the study. 103 patients undergoing coronary bypass graft surgery were recruited. Genotypes were determined with polymerase chain reaction and restriction digestion. Radial artery pressure waveforms were recorded using a calibrated tonometer. Windkessel based diastolic pressure decay analysis was used to generate large (C1) and small (C2) artery compliance values.

The distribution of the genotypes in either gene was in Hardy-Weinberg equilibrium. Homozygosity for the NOS3 polymorphism (894 G→T) was associated with decreased small artery compliance (P=0.01). In contrast the CYBA 242T allele was associated with decreased large artery compliance (P=0.0001). A gene-gene interaction was evident with patients homozygous for the NOS3T allele and possessing the CYBA 242T allele having lower large (P=0.01) and small (P=0.01) artery compliance than patients homozygous for the NOS3 G allele and homozygous for the CYBA C allele.

We confirmed our hypothesis that SNPs in the NOS3 and CYBA genes contribute to vascular compliance.