European Journal of Epidemiology

, Volume 24, Issue 12, pp 763–774 | Cite as

Genetic determinants of serum lipid levels in Chinese subjects: a population-based study in Shanghai, China

  • Gabriella Andreotti
  • Idan Menashe
  • Jinbo Chen
  • Shih-Chen Chang
  • Asif Rashid
  • Yu-Tang Gao
  • Tian-Quan Han
  • Lori C. Sakoda
  • Stephen Chanock
  • Philip S. Rosenberg
  • Ann W. Hsing
GENETIC EPIDEMIOLOGY

Abstract

We examined the associations between 21 single nucleotide polymorphisms (SNPs) of eight lipid metabolism genes and lipid levels in a Chinese population. This study was conducted as part of a population-based study in China with 799 randomly selected healthy residents who provided fasting blood and an in-person interview. Associations between variants and mean lipid levels were examined using a test of trend and least squares mean test in a general linear model. Four SNPs were associated with lipid levels: LDLR rs1003723 was associated with total cholesterol (P-trend = 0.002) and LDL (P-trend = 0.01), LDLR rs6413503 was associated with total cholesterol (P-trend = 0.05), APOB rs1367117 was associated with apoB (P-trend = 0.02), and ABCB11 rs49550 was associated with total cholesterol (P-trend = 0.01), triglycerides (P-trend = 0.01), and apoA (P-trend = 0.01). We found statistically significant effects on lipid levels for LDLR rs6413503 among those with high dairy intake, LPL rs263 among those with high allium vegetable intake, and APOE rs440446 among those with high red meat intake. We identified new associations between SNPs and lipid levels in Chinese previously found in Caucasians. These findings provide insight into the role of lipid metabolism genes, as well as the mechanisms by which these genes may be linked with disease.

Keywords

Single nucleotide polymorphisms Chinese Serum lipid levels 

Notes

Acknowledgements

This research was supported by the Intramural Research Program of the NIH, National Cancer Institute; National Center on Minority Health, NIH; and Center to Reduce Cancer Disparities, NCI, NIH.

Supplementary material

10654_2009_9402_MOESM1_ESM.docx (57 kb)
Supplementary material 1 (DOCX 56 kb)

References

  1. 1.
    Trayhurn P, Beattie JH. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc Nutr Soc. 2001;60:329–39.CrossRefPubMedGoogle Scholar
  2. 2.
    Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356, 222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA. 1986;256:2823–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Wuermli L, Joerger M, Henz S, et al. Hypertriglyceridemia as a possible risk factor for prostate cancer. Prostate Cancer Prostatic Dis. 2005;8:316–20.CrossRefPubMedGoogle Scholar
  4. 4.
    Ruixing Y, Fengping H, Shangling P, et al. Prevalence of hyperlipidemia and its risk factors for the middle-aged and elderly in the Guangxi Hei Yi Zhuang and Han populations. J Investig Med. 2006;54:191–200.CrossRefPubMedGoogle Scholar
  5. 5.
    Andreotti G, Chen J, Gao YT, et al. Serum lipid levels and the risk of biliary tract cancers and biliary stones: a population-based study in China. Int J Cancer. 2008;122:2322–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Heller DA, de Faire U, Pedersen NL, Dahlén G, McClearn GE. Genetic and environmental influences on serum lipid levels in twins. N Engl J Med. 1993;328:1150–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Report of the National Cholesterol Education Progran expert pancel on detection, evaluation and treatment of high blood cholesterol in adults. Arch Intern Med 1988;148:36–69.Google Scholar
  8. 8.
    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;40:189–97.CrossRefPubMedGoogle Scholar
  9. 9.
    Willer CJ, Sanna S, Jackson AU, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet. 2008;40:161–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Sandhu MS, Waterworth DM, Debenham SL, et al. LDL-cholesterol concentrations: a genome-wide association study. Lancet. 2008;371:483–91.CrossRefPubMedGoogle Scholar
  11. 11.
    Linsel-Nitschke P, Götz A, Erdmann J, et al. Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease–a Mendelian Randomisation study. PLoS ONE. 2008;3:e2986.CrossRefPubMedGoogle Scholar
  12. 12.
    Humphries SE, Kessling AM, Horsthemke B, et al. A common DNA polymorphism of the low-density lipoprotein (LDL) receptor gene and its use in diagnosis. Lancet. 1985;1:1003–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986;232:34–47.CrossRefPubMedGoogle Scholar
  14. 14.
    Lopez-Miranda J, Ordovas JM, Ostos MA, et al. Dietary fat clearance in normal subjects is modulated by genetic variation at the apolipoprotein B gene locus. Arterioscler Thromb Vasc Biol. 1997;17:1765–73.PubMedGoogle Scholar
  15. 15.
    Pablos-Méndez A, Mayeux R, Ngai C, Shea S, Berglund L. Association of apo E polymorphism with plasma lipid levels in a multiethnic elderly population. Arterioscler Thromb Vasc Biol. 1997;17(12):3534–41.PubMedGoogle Scholar
  16. 16.
    Aalto-Setala K, Palomaki H, Miettinen H, et al. Genetic risk factors and ischaemic cerebrovascular disease: role of common variation of the genes encoding apolipoproteins and angiotensin-converting enzyme. Ann Med. 1998;30:224–33.CrossRefPubMedGoogle Scholar
  17. 17.
    Boekholdt SM, Peters RJ, Fountoulaki K, Kastelein JJ, Sijbrands EJ. Molecular variation at the apolipoprotein B gene locus in relation to lipids and cardiovascular disease: a systematic meta-analysis. Hum Genet. 2003;113:417–25.CrossRefPubMedGoogle Scholar
  18. 18.
    Liao YC, Lin HF, Rundek T, et al. Multiple genetic determinants of plasma lipid levels in Caribbean Hispanics. Clin Biochem. 2008;41:306–12.CrossRefPubMedGoogle Scholar
  19. 19.
    Andreotti G, Chen J, Gao YT, et al. Polymorphisms of genes in the lipid metabolism pathway and risk of biliary tract cancers and stones: a population-based case-control study in Shanghai, China. Cancer Epidemiol Biomarkers Prev. 2008;17:525–34.CrossRefPubMedGoogle Scholar
  20. 20.
    Licastro F, Porcellini E, Caruso C, Lio D, Corder EH. Genetic risk profiles for Alzheimer’s disease: integration of APOE genotype and variants that up-regulate inflammation. Neurobiol Aging. 2007;28:1637–43.CrossRefPubMedGoogle Scholar
  21. 21.
    Hsing AW, Bai Y, Andreotti G, et al. Family history of gallstones and the risk of biliary tract cancer and gallstones: a population-based study in Shanghai, China. Int J Cancer. 2007;121:832–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Hsing AW, Gao YT, McGlynn KA, et al. Biliary tract cancer and stones in relation to chronic liver conditions: a population-based study in Shanghai, China. Int J Cancer. 2007;120:1981–5.CrossRefPubMedGoogle Scholar
  23. 23.
    Sakoda LC, Gao YT, Chen BE, et al. Prostaglandin-endoperoxide synthase 2 (PTGS2) gene polymorphisms and risk of biliary tract cancer and gallstones: a population-based study in Shanghai, China. Carcinogenesis. 2006;27:1251–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Smith L, Lucas D, Lehnus G. Automated measurement of total cholesterol and triglycerides, in “tandem”, on the discrete sample analyzer, Gilford System 3500. Clin Chem. 1979;25:439–42.PubMedGoogle Scholar
  25. 25.
    National Institutes of Health, National Heart, Lung, and Blood Institute. National Cholesterol Education Program, Recommendations on Lipoprotein Measurement from the Working Group on Lipoprotein Measurement. NIH Publication No.95-3044, September 1995, USA p. 103.Google Scholar
  26. 26.
    Labeur C, Shepherd J, Rosseneu M. Immunological assays of apolipoproteins in plasma: methods and instrumentation. Clin Chem. 1990;36:591–7.PubMedGoogle Scholar
  27. 27.
    Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.PubMedGoogle Scholar
  28. 28.
    Rifai N, Warnick GR, McNamara JR, Belcher JD, Grinstead GF, Frantz ID Jr. Measurement of low-density-lipoprotein cholesterol in serum: a status report. Clin Chem. 1992;38:150–60.PubMedGoogle Scholar
  29. 29.
    Packer BR, Yeager M, Burdett L, et al. SNP500Cancer: a public resource for sequence validation, assay development, and frequency analysis for genetic variation in candidate genes. Nucleic Acids Res. 2006;34(Database issue):D617–21.CrossRefPubMedGoogle Scholar
  30. 30.
    Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–5.CrossRefPubMedGoogle Scholar
  31. 31.
    Stephens M, Donnelly P. A comparison of Bayesian methods for haplotype reconstruction. Am J Hum Genet. 2003;73:1162–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotypes reconstruction from population data. Am J Hum Genet. 2003;68:978–9.CrossRefGoogle Scholar
  33. 33.
    The International HapMap Consortium. The international hapmap project. Nature. 2003;426:789–96.CrossRefGoogle Scholar
  34. 34.
    Davis CL, Wang X, Snieder H, Treiber FA. Genetic and environmental determinants of lipid profile in black and white youth: a study of four candidate genes. Ethn Dis. 2005;15:568–77.PubMedGoogle Scholar
  35. 35.
    Espirito Santo SM, Rensen PC, Goudriaan JR, et al. Triglyceride-rich lipoprotein metabolism in unique VLDL receptor, LDL receptor, and LRP triple-deficient mice. J Lipid Res. 2005;46:1097–102.CrossRefPubMedGoogle Scholar
  36. 36.
    Tacken PJ, Teusink B, Jong MC, et al. LDL receptor deficiency unmasks altered VLDL triglyceride metabolism in VLDL receptor transgenic and knockout mice. J Lipid Res. 2000;41:2055–62.PubMedGoogle Scholar
  37. 37.
    Brown MS, Goldstein JL. How LDL receptors influence cholesterol and atherosclerosis. Sci Am. 1984;251:58–66.PubMedCrossRefGoogle Scholar
  38. 38.
    Pallaud C, Gueguen R, Sass C, et al. Genetic influences on lipid metabolism trait variability within the Stanislas Cohort. J Lipid Res. 2001;42:1879–90.PubMedGoogle Scholar
  39. 39.
    Boland LL, Folsom AR, Boerwinkle E. Apolipoprotein E genotype and gallbladder disease risk in a large population-based cohort. Ann Epidemiol. 2006;16:763–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology. 2004;126:322–42.CrossRefPubMedGoogle Scholar
  41. 41.
    Strautnieks SS, Bull LN, Knisely AS, et al. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet. 1998;20:233–8.CrossRefPubMedGoogle Scholar
  42. 42.
    Noe J, Kullak-Ublick GA, Jochum W, et al. Impaired expression and function of the bile salt export pump due to three novel ABCB11 mutations in intrahepatic cholestasis. J Hepatol. 2005;43:536–43.CrossRefPubMedGoogle Scholar
  43. 43.
    Staels B, Kuipers F. Bile acid sequestrants and the treatment of type 2 diabetes mellitus. Drugs. 2007;67:1383–92.CrossRefPubMedGoogle Scholar
  44. 44.
    Chen WM, Erdos MR, Jackson AU, et al. Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels. J Clin Invest. 2008;118:2620–8.PubMedGoogle Scholar
  45. 45.
    Heizmann C, Kirchgessner T, Kwiterovich PO, et al. DNA polymorphism haplotypes of the human lipoprotein lipase gene: possible association with high density lipoprotein levels. Hum Genet. 1991;86:578–84.CrossRefPubMedGoogle Scholar
  46. 46.
    Merkel M, Eckel RH, Goldberg IJ. Lipoprotein lipase: genetics, lipid uptake, and regulation. J Lipid Res. 2002;43:1997–2006.CrossRefPubMedGoogle Scholar
  47. 47.
    Emi M, Hata A, Robertson M, Iverius PH, Hegele R, Lalouel JM. Lipoprotein lipase deficiency resulting from a nonsense mutation in exon 3 of the lipoprotein lipase gene. Am J Hum Genet. 1990;47:107–11.PubMedGoogle Scholar
  48. 48.
    Minnich A, Kessling A, Roy M, et al. Prevalence of alleles encoding defective lipoprotein lipase in hypertriglyceridemic patients of French Canadian descent. J Lipid Res. 1995;36:117–24.PubMedGoogle Scholar
  49. 49.
    Tsutsumi K, Inoue Y, Shima A, Iwasaki K, Kawamura M, Murase T. The novel compound NO-1886 increases lipoprotein lipase activity with resulting elevation of high density lipoprotein cholesterol, and long-term administration inhibits atherogenesis in the coronary arteries of rats with experimental atherosclerosis. J Clin Invest. 1993;92:411–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Yin W, Tsutsumi K. Lipoprotein lipase activator NO-1886. Cardiovasc Drug Rev. 2003;21:133–42.PubMedGoogle Scholar
  51. 51.
    Yeh YY, Liu L. Cholesterol-lowering effect of garlic extracts and organosulfur compounds: human and animal studies. J Nut. 2001;131:989S–93S.Google Scholar
  52. 52.
    Qureshi AA, Abuirmeileh N, Din ZZ, Elson CE, Burger WC. Inhibition of cholesterol and fatty acid biosynthesis in liver enzymes and chicken hepatocytes by polar fractions of garlic. Lipids. 1983;18:343–8.CrossRefPubMedGoogle Scholar
  53. 53.
    Yeh YY, Yeh SM. Garlic reduces plasma lipids by inhibiting hepatic cholesterol and triacylglycerol synthesis. Lipids. 1994;29:189–93.CrossRefPubMedGoogle Scholar
  54. 54.
    Steinmetz KA, Kushi LH, Bostick RM, Folsom AR, Potter JD. Vegetables, fruit, and colon cancer in the Iowa Women’s Health Study. Am J Epidemiol. 1994;139:1–15.PubMedGoogle Scholar
  55. 55.
    Le Marchand L, Hankin JH, Wilkens LR, Kolonel LN, Englyst HN, Lyu LC. Dietary fiber and colorectal cancer risk. Epidemiology. 1997;8:658–65.CrossRefPubMedGoogle Scholar
  56. 56.
    Chasman DI, Kozlowski P, Zee RY, Kwiatkowski DJ, Ridker PM. Qualitative and quantitative effects of APOE genetic variation on plasma C-reactive protein, LDL-cholesterol, and apoE protein. Genes Immun. 2006;7:211–9.CrossRefPubMedGoogle Scholar
  57. 57.
    Weisgraber KH, Innerarity TL, Mahley RW. Abnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site. J Biol Chem. 1982;257:2518–21.PubMedGoogle Scholar
  58. 58.
    Kowal RC, Herz J, Weisgraber KH, Mahley RW, Brown MS, Goldstein JL. Opposing effects of apolipoproteins E and C on lipoprotein binding to low density lipoprotein receptor-related protein. J Biol Chem. 1990;265:10771–9.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Gabriella Andreotti
    • 1
  • Idan Menashe
    • 1
  • Jinbo Chen
    • 2
  • Shih-Chen Chang
    • 3
  • Asif Rashid
    • 4
  • Yu-Tang Gao
    • 5
  • Tian-Quan Han
    • 6
  • Lori C. Sakoda
    • 7
  • Stephen Chanock
    • 1
    • 8
    • 9
  • Philip S. Rosenberg
    • 1
  • Ann W. Hsing
    • 1
  1. 1.Division of Cancer Epidemiology and GeneticsNational Cancer Institute, National Institutes of Health, DHHSBethesdaUSA
  2. 2.Department of Biostatistics and EpidemiologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.Department of Discovery Medicine and EpidemiologyAstraZenecaWilmingtonUSA
  4. 4.Department of PathologyM.D. Anderson Cancer CenterHoustonUSA
  5. 5.Department of EpidemiologyShanghai Cancer InstituteShanghaiChina
  6. 6.Department of Surgery, Ruijin HospitalSecond Medical UniversityShanghaiChina
  7. 7.Department of EpidemiologyUniversity of WashingtonSeattleUSA
  8. 8.Core Genotyping FacilityNational Cancer Institute, National Institutes of HealthGaithersburgUSA
  9. 9.Pediatric Oncology Branch, Center for Cancer ResearchNational Cancer Institute, National Institutes of HealthBethesdaUSA

Personalised recommendations