Endocrine Abstracts (2006) 11 P306

The variable number of tandem repeat polymorphism in the NOS3 gene is associated with arterial compliance and insulin resistance in coronary artery disease

RS Drummond1, HHC Koh-Tan1, NJR Brain1, A Kirk2, N Sattar1, JMC Connell1 & AF Dominiczak1


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


A common NOS3 polymorphism (the gene which encodes endothelial nitric oxide synthase), a variable number of tandem repeats within Intron 4 has been associated with cardiovascular disorders in which nitric oxide bioactivity is impaired including myocardial infraction. Consistent characteristic changes in the pressure pulse wave shape have been associated with ageing, risk factors for cardiovascular disease and impaired NO bioactivity. Therefore pulse waveform analysis can be utilized to quantify arterial compliance as well as dynamic changes in NO bioactivity. Parameters associated with Insulin resistance have also been associated with both arterial stiffness and ischaemic heart disease. We hypothesise that this polymorphism within NOS3 would influence vascular compliances and parameters of insulin resistance in patients with coronary artery disease.

Ethical approval was obtained from the local committee. We recruited 101 patients with angiographically documented coronary artery disease. Genotypes were determined with polymerase chain reaction and restriction digestion. Radial artery pressure waveforms were recorded using a calibrated tonometer at the radial artery to derive a measurement of systemic arterial compliance (augmentation index). Moreover we measured biochemical parameters associated with insulin resistance: ICAM, IL-6 and sensitive CRP. Differences between genotype groups were analysed using unequal variance unpaired Student’s t tests.

The distribution of the genotypes in did not differ significantly from that expected under Hardy Weinberg equilibrium. We found that the AA subtype was associated with increased systemic arterial stiffness (P=0.03), and higher levels of biochemical parameters associated with biochemical parameters of insulin resistance including CRP (P=0.01), IL 6 (P=0.04) and ICAM (P=0.05).

We confirmed our hypothesis that this polymorphism of the NOS3 gene affects arterial compliance and biochemical parameters of insulin resistance.

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