Skip to main content

Effects of SNPs at newly identified lipids loci on blood lipid levels and risk of coronary heart disease in Chinese Han population: A case control study

Journal of Huazhong University of Science and Technology [Medical Sciences] volume 31, pages 452–456 (2011)Cite this article

Summary

Associations between “lipid-related” candidate genes, blood lipid concentrations and coronary artery disease (CHD) risk are not clear. We aimed to investigate the effect of three newly identified lipids loci from genome-wide association studies on CHD and blood lipid levels in Chinese Han population. The genotypes of SNPs at three newly identified lipid loci and blood lipids concentrations were examined in 1360 CHD patients and 1360 age- and sex-frequency matched controls from an unrelated Chinese Han population. Allele T of rs16996148 occurred less frequently in CHD patients with the odds ratio (OR) being 0.64 (95% CI 0.50 to 0.81), after adjusting for conventional risk factors and was associated with a 33% decreased CHD risk (P<0.01) comparing with the major allele G. Individuals with GT genotype had the lowest CHD risk. No associations were found between the polymorphisms of other two loci with CHD risk and all three SNPs had no effect on lipid profile in this population. SNP rs16996148 on chromosome 19p13 is significantly associated with lower risk for CHD in Chinese Han population. However, it remains unresolved why these lipid-related loci had significantly less effects than the correspondingly expected effects on blood lipids levels in this population.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

39,95 €

Price includes VAT (Finland)

References

  1. Pilia G, Chen WM, Scuteri A, et al. Heritability of cardiovascular and personality traits in 6148 Sardinians. PLoS Genet, 2006,2(8):e132

    Article  PubMed  Google Scholar 

  2. Heller DA, U. de Faire, Pedersen NL, et al. Genetic and environmental influences on serum lipid levels in twins. N Engl J Med, 1993,328(16):1150–1156

    Article  PubMed  CAS  Google Scholar 

  3. Pollin TI, Hsueh WC, Steinle NI, et al. A genome-wide scan of serum lipid levels in the Old Order Amish. Atherosclerosis, 2004,173(1):89–96

    Article  PubMed  CAS  Google Scholar 

  4. Kuulasmaa K, Tunstall-Pedoe H, Dobson A, et al. Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations. Lancet, 2000,355(9205):675–687

    Article  PubMed  CAS  Google Scholar 

  5. Knoblauch H, Bauerfeind A, Toliat MR. Haplotypes and SNPs in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol. Human Molecular Genetics, 2004,13(10):993–1004

    Article  PubMed  CAS  Google Scholar 

  6. Lusis AJ, Fogelman AM, Fonarow GC. Genetic basis of atherosclerosis, part II: clinical implications. Circulation, 2004,110:2066–2071

    Article  PubMed  Google Scholar 

  7. Lusis AJ, Mar R, Pajukanta P. Genetics of atherosclerosis. Annu Rev Genomics Hum Genet, 2004,5:189–218

    Article  PubMed  CAS  Google Scholar 

  8. Breslow JL. Genetics of lipoprotein abnormalities associated with coronary artery disease susceptibility. Annu Rev Genet, 2000,34:233–254

    Article  PubMed  CAS  Google Scholar 

  9. Chasman DI, Pare G, Zee RY, et al. Genetic loci associated with plasma concentration of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B among 6382 white women in genome-wide analysis with replication. Circ Cardiovasc Genet, 2008,1:21–30

    Article  PubMed  CAS  Google Scholar 

  10. Corbo RM, Vilardo T, Ruggeri M, et al. Apolipoprotein E genotype and plasma levels in coronary artery disease. A case-control study in the Italian population. Clin Biochem, 1999,32(3):217–222

    Article  PubMed  CAS  Google Scholar 

  11. Brazier L, Tiret L, Luc G, et al. Sequence polymorphisms in the apolipoprotein(a) gene and their association with lipoprotein(a) levels and myocardial infarction. The ECTIM study. Atherosclerosis, 1999,144():323–333

    Article  CAS  Google Scholar 

  12. Scott LJ, Mohlke KL, Bonnycastle LL, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science, 2007,316(5829):1341–1345

    Article  PubMed  CAS  Google Scholar 

  13. Scuteri A, Sanna S, Chen WM, et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity related traits. PLoS Genet, 2007,3(7):e115

    Article  PubMed  Google Scholar 

  14. Saxena R, Voight BF, Lyssenko V, et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science, 2007,316:1331–1336

    Article  PubMed  CAS  Google Scholar 

  15. Kathiresan S, Melander O, Guiducci C, et al. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet, 2008,40(2):189–197

    Article  PubMed  CAS  Google Scholar 

  16. Willer CJ, Sannal S, Jackson AU, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet, 2008,40(2):161–169

    Article  PubMed  CAS  Google Scholar 

  17. Tai ES, Sim XL, Ong TH, et al. Polymorphisms at newly identified lipid associated loci are associated with blood lipids and cardiovascular disease in an Asian Malay population. J Lipid Res, 2009,50:514–520

    Article  PubMed  CAS  Google Scholar 

  18. Nomenclature and criteria for diagnosis of ischemic heart disease. Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. Circulation, 1979,59(3):607–609

    Google Scholar 

  19. Zhou L, Zhang XM, He MA, et al. Associations between single nucleotide polymorphisms on chromosome 9p21 and risk of coronary heart disease in Chinese Han population. Arterioscler Thromb Vasc Biol, 2008,28(11):2085–2089

    Article  PubMed  CAS  Google Scholar 

  20. Rauch U, Feng K, Zhou XH. Neurocan: a brain chondroitin sulfate proteoglycan. Cell Mol Life Sci, 2001,58(12–13):1842–1856

    Article  PubMed  CAS  Google Scholar 

  21. Keavney B, Palmer A, Parish S, et al. Lipid-related genes and myocardial infarction in 4685 cases and 3460 controls: discrepancies between genotype, blood lipid concentrations, and coronary disease risk. Int J Epidemiol, 2004,33(5):1002–1013

    Article  PubMed  Google Scholar 

  22. Verges B. Lipid modification in type 2 diabetes: the role of LDL and HDL. Fundam Clin Pharmacol, 2009,23(6): 681–685

    Article  PubMed  CAS  Google Scholar 

  23. Taskinen MR. Type 2 diabetes as a lipid disorder. Curr Mol Med, 2005,5(3):297–308

    Article  PubMed  CAS  Google Scholar 

  24. Miyata M, Smith JD. Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and betaamyloid peptides. Nat Genet, 1996,14(1):55–61

    Article  PubMed  CAS  Google Scholar 

  25. Davignon J. Apolipoprotein E polymorphism and atherosclerosis. In: Schwartz CJ, Born GVR (eds). New Horizons in Coronary Heart Disease, London: Current Science, 1993:5.1–5.21

    Google Scholar 

  26. Cullen P, Cignarella A, Brennhausen B, et al. Phenotype-dependent differences in apolipoprotein E metabolism and in cholesterol homeostasis in human monocyte-derived macrophages. J Clin Invest, 1998,101(8): 1670–1677

    Article  PubMed  CAS  Google Scholar 

  27. Riddell DR, Graham A, Owen JS. Apolipoprotein E inhibits platelet aggregation through the L-arginine:nitric oxide pathway-Implications for vascular disease. J Biol Chem, 1997,272(1):89–95

    Article  PubMed  CAS  Google Scholar 

  28. Kelly ME, Clay MA, Mistry MJ, et al. Apolipoprotein E inhibition of proliferation of mitogen-activated T lymphocytes: production of interleukin-2 with reduced biological activity. Cell Immunol, 1994,159(2):124–139

    Article  PubMed  CAS  Google Scholar 

  29. Zondervan KT, Cardon LR. The complex interplay among factors that influence allelic association. Nat Rev Genet, 2004,5:89–100

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Ke Zhuang  (壮 可), Wencai Zhang  (张文才), Xiaobo Zhang  (张晓博), Fangqin Wu  (吴芳琴) & Longxian Cheng  (程龙献)

Authors
  1. Ke Zhuang  (壮 可)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wencai Zhang  (张文才)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaobo Zhang  (张晓博)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fangqin Wu  (吴芳琴)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Longxian Cheng  (程龙献)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Longxian Cheng  (程龙献).

Additional information

This project was supported by grants from the National Natural Sciences Foundation of China (No. 30525031 and No. 30430590).

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zhuang, K., Zhang, W., Zhang, X. et al. Effects of SNPs at newly identified lipids loci on blood lipid levels and risk of coronary heart disease in Chinese Han population: A case control study. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 31, 452–456 (2011). https://doi.org/10.1007/s11596-011-0472-6

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-011-0472-6

Key words

  • coronary heart disease
  • blood lipids
  • lipid loci
  • single nucleotide polymorphism
  • Chinese Han population