All Title Author
Keywords Abstract

PLOS ONE  2011 

Genetic Variants at Newly Identified Lipid Loci Are Associated with Coronary Heart Disease in a Chinese Han Population

DOI: 10.1371/journal.pone.0027481

Full-Text   Cite this paper   Add to My Lib

Abstract:

Background Recent genome-wide association studies (GWAS) have mapped several novel loci influencing blood lipid levels in Caucasians. We sought to explore whether the genetic variants at newly identified lipid-associated loci were associated with CHD susceptibility in a Chinese Han population. Methodology/Principal Findings We conducted a two-stage case-control study in a Chinese Han population. The first-stage, consisting of 1,376 CHD cases and 1,376 sex and age- frequency matched controls, examined 5 novel lipid-associated single-nucleotide polymorphisms (SNPs) identified from GWAS among Caucasians in relation to CHD risk in Chinese. We then validated significant SNPs in the second-stage, consisting of 1,269 cases and 2,745 controls. We also tested associations between SNPs within the five novel loci and blood lipid levels in 4,121 controls. We identified two novel SNPs (rs599839 in CELSR2-PSRC1-SORT1 and rs16996148 in NCAN-CILP2) that were significantly associated with reduced CHD risk in Chinese (odds ratios (95% confidence intervals) in the dominant model 0.76 (0.61-0.90; P = 0.001), 0.67 (0.57-0.77; P = 3.4×10?8), respectively). Multiple linear regression analyses using dominant model showed that rs599839 was significantly associated with decreased LDL levels (P = 0.022) and rs16996148 was significantly associated with increased LDL and HDL levels (P = 2.9×10?4 and 0.001, respectively). Conclusions/Significance We identified two novel SNPs (rs599839 and rs16996148) at newly identified lipid-associated loci that were significantly associated with CHD susceptibility in a Chinese Han population.

References

[1]  Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, et al. (2010) Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 121: e46–e215.
[2]  Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med; 3: e442.
[3]  Murray CJ, Lopez AD (1997) Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 349: 1436–1442.
[4]  Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, et al. (2011) Heart Disease and Stroke Statistics--2011 Update: A Report From the American Heart Association. Circulation 123(4): e18–e209.
[5]  Clarke R, Emberson JR, Parish S, Palmer A, Shipley M, et al. (2007) Cholesterol fractions and apolipoproteins as risk factors for heart disease mortality in older men. Arch Intern Med 167: 1373–1378.
[6]  Kuulasmaa K, Tunstall-Pedoe H, Dobson A, Fortmann S, Sans S, et al. (2000) Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations. Lancet 355: 675–687.
[7]  Law MR, Wald NJ, Rudnicka AR (2003) Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. Bmj 326: 1423.
[8]  Breslow JL (2000) Genetics of lipoprotein abnormalities associated with coronary artery disease susceptibility. Annu Rev Genet 34: 233–254.
[9]  Pilia G, Chen WM, Scuteri A, Orru M, Albai G, et al. (2006) Heritability of cardiovascular and personality traits in 6,148 Sardinians. PLoS Genet 2: e132.
[10]  Pollin TI, Hsueh WC, Steinle NI, Snitker S, Shuldiner AR, et al. (2004) A genome-wide scan of serum lipid levels in the Old Order Amish. Atherosclerosis 173: 89–96.
[11]  Kathiresan S, Melander O, Anevski D, Guiducci C, Burtt NP, et al. (2008) Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med 358: 1240–1249.
[12]  Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, et al. (2007) Genomewide association analysis of coronary artery disease. N Engl J Med 357: 443–453.
[13]  Aulchenko YS, Ripatti S, Lindqvist I, Boomsma D, Heid IM, et al. (2009) Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet 41: 47–55.
[14]  Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, et al. (2008) Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet 40: 189–197.
[15]  Kathiresan S, Willer CJ, Peloso GM, Demissie S, Musunuru K, et al. (2009) Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 41: 56–65.
[16]  Sandhu MS, Waterworth DM, Debenham SL, Wheeler E, Papadakis K, et al. (2008) LDL-cholesterol concentrations: a genome-wide association study. Lancet 371: 483–491.
[17]  Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, et al. (2008) Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 40: 161–169.
[18]  Law SW, Lackner KJ, Fojo SS, Hospattankar A, Monge JC, et al. (1986) The molecular biology of human apoA-I, apoA-II, apoC-II and apoB. Adv Exp Med Biol 201: 151–162.
[19]  Sing CF, Davignon J (1985) Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet 37: 268–285.
[20]  Muendlein A, Geller-Rhomberg S, Saely CH, Winder T, Sonderegger G, et al. (2009) Significant impact of chromosomal locus 1p13.3 on serum LDL cholesterol and on angiographically characterized coronary atherosclerosis. Atherosclerosis 206: 494–499.
[21]  Samani NJ, Braund PS, Erdmann J, Gotz A, Tomaszewski M, et al. (2008) The novel genetic variant predisposing to coronary artery disease in the region of the PSRC1 and CELSR2 genes on chromosome 1 associates with serum cholesterol. J Mol Med 86: 1233–1241.
[22]  Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, et al. (2010) From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 466: 714–719.
[23]  Tai ES, Sim XL, Ong TH, Wong TY, Saw SM, et al. (2009) Polymorphisms at newly identified lipid-associated loci are associated with blood lipids and cardiovascular disease in an Asian Malay population. J Lipid Res 50: 514–520.
[24]  Zhou L, Zhang X, He M, Cheng L, Chen Y, et al. (2008) Associations between single nucleotide polymorphisms on chromosome 9p21 and risk of coronary heart disease in Chinese Han population. Arterioscler Thromb Vasc Biol 28: 2085–2089.
[25]  Puavilai G, Chanprasertyotin S, Sriphrapradaeng A (1999) Diagnostic criteria for diabetes mellitus and other categories of glucose intolerance: 1997 criteria by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (ADA), 1998 WHO consultation criteria, and 1985 WHO criteria. World Health Organization. Diabetes Res Clin Pract 44: 21–26.

Full-Text

comments powered by Disqus