P2.38 The Anril Locus on Chromosome 9P21 Affects Stiffness of the Abdominal Aorta

Abstract

Coronary artery disease (CAD) is the leading cause of death worldwide. Recently, several genome wide association studies have reported associations between a region on chromosome 9p21 and a broad range of arterial diseases, including CAD and intracranial aneurysms. However, no clear associations with intermediate phenotypes have been described. In order to investigate the possible influence of the CAD-associated SNPs on arterial wall integrity, we analyzed associations between SNPs and stiffness of the abdominal aorta.

400 subjects, 212 men and 188 women (70–88 years) were studied. The pulsatile diameter of the abdominal aorta was examined at the midpoint between the renal arteries and the bifurcation, using a wall track system. Blood pressure was taken from the brachial artery (Dinamap). Two CAD- and aneurysm-associated SNPs (rs10757274 and rs2891168) and one T2D-associated SNP (rs1081161) within the 9p21 region were genotyped. Aortic stiffness was decreased in male carriers of the rs10757274G and rs2891168G alleles. Accordingly, aortic compliance and distensibility were higher in men who carried the rs10757274G and rs2891168G alleles. Adjustment for age and mean arterial pressure had no effect on these associations. None of the SNPs were associated with either intima-media thickness or lumen diameter of the abdominal aorta. There were no associations between the T2D-associated rs10811661 SNP and any measure of aortic stiffness.

Impaired mechanical properties of the aortic wall may be a link between the association between chromosome 9p21 polymorphisms and vascular disease.