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

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

doi:10.1194/jlr.m800456-jlr200

Abstract

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.

Highlights

We conducted a cross-sectional study of Malay participants aged 40–80 years (n 5 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
Through genome-wide association studies, we and others have identified single-nucleotide polymorphisms (SNPs) at six novel loci associated with blood lipid concentrations [3,4,5,6] and coronary heart disease (CHD) [6]
The importance of studying these other ethnic groups becomes apparent when we examine the epidemiology of CVDs in the world today [7]

Summary

Introduction

We conducted a cross-sectional study of Malay participants aged 40–80 years (n 5 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. 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 5 0.005) and lower LDL-C (P 5 0.048), respectively 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. Through genome-wide association studies, we and others have identified single-nucleotide polymorphisms (SNPs) at six novel loci associated with blood lipid concentrations [3,4,5,6] and CHD [6] These observations were made primarily in individuals of European ancestry. This article is available online at http://www.jlr.org allow us to assess the association between the presence of these polymorphisms and the risk of CVD

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Conclusion