on August 13, 2009
Published online before print August 13, 2009, doi: 10.1161/STROKEAHA.109.556563
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 28, 2009
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. * To whom correspondence should be addressed. 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 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<P Conclusion—This initial multi-ethnic high-density association study of carotid IMT suggests some novel loci requiring further evaluation in follow-up studies.
Revised on June 19, 2009
Accepted on July 10, 2009
Multi-Ethnic Genetic Association Study of Carotid Intima-Media Thickness Using a Targeted Cardiovascular SNP Microarray
Matthew B. Lanktree BSc;
50 000 SNPs, densely mapping 2100 genes found on the gene-centric Illumina cardiovascular disease beadchip in a multi-ethnic population-based sample.
0.05).
Key words: atherosclerosis • cardiovascular disease • genetics • carotid intima-media thickness • ultrasonography