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Novel genetic variants linked to coronary artery disease by genome-wide association are not associated with carotid artery intima-media thickness or intermediate risk phenotypes

Lookup NU author(s): Dr Michael Cunnington, Dr Darroch Hall, Dr Peter Avery, Hannah Watkins, Professor Bernard Keavney


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Background: It is uncertain whether the novel single nucleotide polymorphisms (SNPs) that have recently been associated with coronary artery disease (CAD) in genome-wide studies also influence carotid atheroma and stroke risk. The mechanisms of their association with CAD are unknown; relationships to other cardiovascular phenotypes may give mechanistic clues. Carotid artery intima-media thickness (CIMT) is a subclinical marker of atherosclerosis associated with stroke. We investigated association of reported CAD risk variants with CIMT, and with other intermediate phenotypes that may implicate causative pathways. Methods: We Studied 1425 members of 248 British Caucasian families ascertained through a hypertensive proband. We genotyped CAD risk SNPs on chromosomes 9 (rs 1333049, rs7044859, rs496892, rs7865618), 6 (rs6922269) and 2 (rs2943634) using TaqMan. Merlin software was used for faintly-based association testing. Results: No significant association was found between genotype at any SNP and CIMT in 846 individuals with acceptable measurements. Nor were SNPs significantly associated with blood pressure, obesity, cholesterol, CRP, interleukin-6, TNF-alpha, or leptin. Conclusions: These novel CAD variants are not associated with CIMT and do not appear to mediate the risk of atherothrombosis through known risk factors. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Publication metadata

Author(s): Cunnington MS, Mayosi BM, Hall DH, Avery PJ, Farrall M, Vickers MA, Watkins H, Keavney B

Publication type: Letter

Publication status: Unknown

Journal: Atherosclerosis

Year: 2009

Volume: 203

Issue: 1

Pages: 41-44

ISSN (print): 0021-9150

ISSN (electronic): 1879-1484



DOI: 10.1016/j.atherosclerosis.2008.06.025