Association of genetic variation on chromosome 9p21.3 and arterial stiffness

Abstract

Objective. Genome wide association studies have consistently reported associations between a region on chromosome 9p21.3 and a broad range of vascular diseases such as coronary artery disease (CAD), aortic and intracranial aneurysms and type-2 diabetes (T2D). However, clear associations with intermediate phenotypes have not been described so far. To shed light on a possible influence of this chromosomal region on arterial wall integrity, we analyzed associations between single nucleotide polymorphisms (SNPs) and degree of stiffness of the abdominal aorta in elderly individuals. Methods and Results.A total of 400 subjects, 212 men and 188 women, aged 70-88 years were included. Arterial stiffness was examined at the midpoint between the renal arteries and the aortic bifurcation. Two CAD-and aneurysm-associated SNPs (rs10757274 and rs2891168) and one T2D-associated SNP (rs1081161) within the 9p21.3 region were genotyped. Aortic compliance and distensibility coefficients were higher in carriers of the rs10757274G and rs2891168G alleles in men reflecting a decrease in aortic stiffness. Adjustment for age and mean arterial pressure had no effect on these associations. The two SNPs were not associated with intima-media thickness or lumen diameter of the abdominal aorta. There were no associations between the rs10811661 SNP and any measure of aortic stiffness.Conclusions. Impaired mechanical properties of the arterial wall may explain the association between chromosome 9p21.3 polymorphisms and vascular disease.

P4.04 Impaired Abdominal Aortic Wall Integrity in Elderly Men Carrying the Angiotensin-Converting Enzyme D-Allele

“…are of importance. 8 We have previously reported an association of aneurysm-associated genetic variations on chromosome 9p21.3 with reduced abdominal aortic stiffness, 26 while this study showed higher stiffness in carriers of the D allele. Deranged abdominal aortic stiffness indicates impaired integrity of the aortic wall which might be important in aneurysmal disease.…”

Gene polymorphisms associated with susceptibility to coronary artery disease in Han Chinese people

“…However, the mechanisms by which these alleles affect the incidence of CAD remain to be elucidated (Shen et al, 2008b;Ding et al, 2009;Scheffold et al, 2011). Some authors have suggested that these polymorphisms may impair the mechanical properties of the arterial wall and thus influence vascular diseases (Bjorck et al, 2009). In our study, rs10757274G was not significantly associated with CAD in the population we selected (P = 0.08); this observation may be related to sample size and individual susceptibility.…”

A genome-wide association study of the association between single nucleotide polymorphisms and brachial-ankle pulse wave velocity in healthy Koreans

“…However, the pathophysiological links between the genetic and physiological components remain largely unknown [26,33,34]. In addition, some studies have reported that SNPs can affect arterial stiffness [8]; examples include SNPs in genes such as those encoding the renin-angiotensin-aldosterone system, matrix protein/metalloproteinases, the nitric oxide pathway, b-adrenergic/endothelin receptors, the inflammatory cascade, and others [35][36][37][38][39].…”