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Papers In Press, published online ahead of print March 1, 2009
J. Lipid Res., doi:10.1194/jlr.M800456-JLR200

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Journal of Lipid Research, Vol. 50, 514-520, March 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Polymorphisms at newly identified lipid-associated loci are associated with blood lipids and cardiovascular disease in an Asian Malay population

E. Shyong Tai^1,*, Xue Ling Sim, Twee Hee Ong, Tien Yin Wong^**,, Seang Mei Saw^**,, Tin Aung^**, Sekar Kathiresan^***, Marju Orho-Melander, Jose M. Ordovas, Jonathan T. Tan and Mark Seielstad

^* Department of Endocrinology, Singapore General Hospital, Singapore, National University of Singapore, Singapore
Center for Molecular Epidemiology, National University of Singapore, Singapore
^** Singapore Eye Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Department of Community Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Genome Institute of Singapore, Singapore
Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia
^*** Cardiology Division, Massachusetts General Hospital, Boston, MA
Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, Sweden
Nutrition and Genomics Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of two tables.

This study was supported by the National Medical Research Council, Grants 0796/2003, 0863/2004, and CSI/0002/2005, and Biomedical Research Council Grant 501/1/25-5. Additional support was provided by the Genome Institute of Singapore, the Singapore Tissue Network, and the Ministry of Health, Singapore.

Published, JLR Papers in Press, November 5, 2008.

¹ To whom correspondence should be addressed. e-mail: eshyong{at}pacific.net.sg

We conducted a cross-sectional study of Malay participants aged 40–80 years (n = 2,932) to examine the associations between polymorphisms at newly identified, lipid-associated loci with blood lipid levels and prevalent cardiovascular disease (CVD) in a Malay population in Asia. A polymorphism adjacent to the TRIB1 locus (rs17321515) was associated with elevated total cholesterol and LDL-cholesterol (LDL-C) after adjustment for age and sex (both P values <0.007) and with increased risk of coronary heart disease and CVD [odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.03–1.46; and OR 1.2, 95% CI 1.02–1.42, respectively] under an additive model of inheritance. In addition, using recessive models of inheritance, polymorphisms on chromosome 19 adjacent to the CILP2 and PBX4 loci (rs16996148) and on chromosome 1 at the GALNT2 locus (rs4846914) were associated with elevated HDL-C (P = 0.005) and lower LDL-C (P = 0.048), respectively. Although novel, the former is consistent with the association between this polymorphism and lower blood triglycerides observed in the initial studies conducted in populations of European ancestry. Neither showed statistically significant association with CVD. These observations should form the basis of further investigation to identify the causative polymorphisms at this locus, and also to understand the mechanistic roles that this protein may play in lipoprotein metabolism in Asians and other populations.

Supplementary key words genetics • ethnic group • coronary heart disease

Abbreviations: CHD, coronary heart disease; CVD, cardiovascular disease; SNP, single-nucleotide polymorphism

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