Polymorphisms at newly identified lipid-associated loci are associated with blood lipids and cardiovascular disease in an Asian Malay population.
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.
Tai
E Shyong
ES
Department of Endocrinology, Singapore General Hospital, Singapore, National University of Singapore, Singapore. Electronic address: eshyong@pacific.net.sg.
Sim
Xue Ling
XL
Center for Molecular Epidemiology, National University of Singapore, Singapore.
Ong
Twee Hee
TH
Genome Institute of Singapore, Singapore.
Wong
Tien Yin
TY
Singapore Eye Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia.
Saw
Seang Mei
SM
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.
Aung
Tin
T
Singapore Eye Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Kathiresan
Sekar
S
Cardiology Division, Massachusetts General Hospital, Boston, MA.
Orho-Melander
Marju
M
Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, Sweden.
Ordovas
Jose M
JM
Nutrition and Genomics Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
Tan
Jonathan T
JT
Center for Molecular Epidemiology, National University of Singapore, Singapore.
Seielstad
Mark
M
Genome Institute of Singapore, Singapore.
D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D002784:Cholesterol / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008055:Lipids / Q000097:blood* / Q000235:genetics*; D008296:Malaysia / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000037:antagonists & inhibitors; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology
D008078:Cholesterol, LDL; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; C493170:TRIB1 protein, human; D002784:Cholesterol; D017346:Protein Serine-Threonine Kinases