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(Stroke. 2009;40:3173.)
© 2009 American Heart Association, Inc.

Original Contributions

Multi-Ethnic Genetic Association Study of Carotid Intima-Media Thickness Using a Targeted Cardiovascular SNP Microarray

Matthew B. Lanktree, BSc; Robert A. Hegele, MD; Salim Yusuf, MD, PhD Sonia S. Anand, MD, PhD

From the Robarts Research Institute and Schulich School of Medicine & Dentistry (M.B.L., R.A.H.), University of Western Ontario, London, Ontario, Canada; and Population Health Research Institute, Hamilton Health Sciences (S.Y., S.S.A.), and the Departments of Medicine and Clinical Epidemiology, McMaster University (S.Y., S.S.A.), Hamilton, Ontario, Canada.

Correspondence to Robert A. Hegele, MD, FRCPC, FACP, Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, London, Ontario, Canada, N6A 5K8. E-mail hegele{at}robarts.ca

Background and Purpose— Identification of subclinical atherosclerosis by ultrasonographic measurement of carotid intima-media thickness (IMT) is a validated tool, in conjunction with traditional risk factors, for clinical assessment of cardiovascular disease risk. IMT has also been recognized as a quantitative measure of cardiovascular disease progression in asymptomatic individuals, and many candidate gene association studies have attempted to identify genetic variants associated with interindividual differences in IMT with limited success. We sought to test the association between subclinical atherosclerosis measured by IMT and 50 000 SNPs, densely mapping 2100 genes found on the gene-centric Illumina cardiovascular disease beadchip in a multi-ethnic population-based sample.

Methods— IMT was measured by B-mode ultrasound and DNA was collected from a population-based sample of South Asian (n=328), Chinese (n=302), and European Caucasian (n=268) participants. Genetic association was measured using multivariate linear regression including adjustment for covariates.

Results— The most robust association across all models tested was observed for a SNP (rs3791398) in histone deacetylase 4 (HDAC4; P=1.8e-5 to P=3.6e-5), while another strong association signal was observed with natriuretic peptide receptor a/guanylate cyclase A (NPR1) (rs10082235, P=5.4e-5). Seven of 13 previously reported functional candidate genes contained a SNP that was marginally associated (0.01<P0.05).

Conclusion— This initial multi-ethnic high-density association study of carotid IMT suggests some novel loci requiring further evaluation in follow-up studies.

Key Words: atherosclerosis • cardiovascular disease • genetics • carotid intima-media thickness • ultrasonography