Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Linkage of high-density lipoprotein–cholesterol concentrations to a locus on chromosome 9p in Mexican Americans

Abstract

High-density lipoproteins (HDLs) are anti-atherogenic lipoproteins that have a major role in transporting cholesterol from peripheral tissues to the liver, where it is removed1,2. Epidemiologic studies have shown that low levels of high-density lipoprotein–cholesterol (HDL-C) are associated with an increased incidence of coronary heart disease and an increased mortality rate3,4, indicating a protective role of high concentrations of HDL-C against atherogenesis and the development of coronary heart disease. HDL-C level is influenced by several genetic and nongenetic factors3,5. Nongenetic factors include smoking, which has been shown to decrease the HDL-C level. Exercise and alcohol have been shown to increase HDL-C levels6,7. Decreased HDL-C is often associated with other coronary heart disease risk factors such as obesity, hyperinsulinemia and insulin resistance, hypertriglyceridemia and hypertension3. Although several genes have been identified for rare forms of dyslipidemia, the genes accounting for major variation in HDL-C levels have yet to be identified8. Using a multipoint variance components linkage approach, we found strong evidence of linkage (lod score=3.4; P=0.00004) of a quantitative trait locus (QTL) for HDL-C level to a genetic location between markers D9S925 and D9S741 on chromosome 9p in Mexican Americans. A replication study in an independent set of Mexican American families confirmed the existence of a QTL on chromosome 9p.

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

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Rosenson, R.S. Beyond low-density lipoprotein cholesterol. Arch. Intern. Med. 156, 1278–1284 (1996).

    Article  CAS  Google Scholar 

  2. Luoma, P.V. Gene activation, apolipoprotein A-I/high density lipoprotein, atherosclerosis prevention and longevity. Pharmacol. Toxicol. 81, 57–64 (1997).

    Article  CAS  Google Scholar 

  3. Calabresi, L. & Franceschini, G. High density lipoprotein and coronary heart disease: insights from mutations leading to low high density lipoprotein. Curr. Opin. Lipidol. 8, 219–224 (1997).

    Article  CAS  Google Scholar 

  4. Gordon, D.J. Factors affecting high-density lipoproteins. Endocr. Metab. Clin. North. Am. 27, 699–709 (1998).

    Article  CAS  Google Scholar 

  5. Wilt, V.M. & Gums, J.G. 'Isolated' low high-density lipoprotein cholesterol. Ann. Pharmacother. 31, 89–97 (1996).

    Article  Google Scholar 

  6. Thompson, P.D. et al. High density lipoprotein metabolism in endurance athletes and sedentary men. Circulation 84, 140–152 (1991).

    Article  CAS  Google Scholar 

  7. Weidner, G. et al. Sex differences in high-density lipoprotein cholesterol among low-level alcohol consumers. Circulation 83, 176–180 (1991).

    Article  CAS  Google Scholar 

  8. Hegele, R.A. Monogenic dyslipidemias: window on determinants of plasma lipoprotein metabolism. Am. J. Hum. Genet. 69, 1161–1177 (2001).

    Article  CAS  Google Scholar 

  9. Mitchell, B.D. et al. Genetic and environmental contributions to cardiovascular risk factors in Mexican Americans. Circulation 94, 2159–2170 (1996).

    Article  CAS  Google Scholar 

  10. Blangero, J. & Almasy, L. Multipoint oligogenic linkage analysis of quantitative traits. Genet. Epidemiol. 14, 959–964 (1997).

    Article  CAS  Google Scholar 

  11. MacCluer, J.W. et al. Genetics of atherosclerosis risk factors in Mexican Americans. Nutr. Rev. 57, S59–S65 (1999).

  12. Kruglyak, L. & Lander, E.S. High-resolution genetic mapping of complex traits. Am. J. Hum. Genet. 56, 1212–1223 (1995).

    CAS  Google Scholar 

  13. Dupuis, J. & Siegmund, D. Statistical methods for mapping quantitative trait loci from a dense set of markers. Genetics 151, 373–386 (1999).

    CAS  Google Scholar 

  14. Hauser, E.R. & Boehnke, M. Confirmation of linkage results in affected-sib-pair linkage analysis for complex genetic traits. Am. J. Hum. Genet. 61, A278 (1997).

  15. Roberts, S.B., MacLean, C.J., Neale, M.C., Eaves, L.J. & Kendler, K.S. Replication of linkage studies of complex traits: an examination of variation in location estimates. Am. J. Hum. Genet. 65, 876–884 (1999).

    Article  CAS  Google Scholar 

  16. Lander, E. & Kruglyak, L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet. 11, 241–247 (1995).

    Article  CAS  Google Scholar 

  17. Owerbach, D. et al. Leukocyte and fibroblast interferon genes are located on human chromosome 9. Proc. Natl Acad. Sci. USA 78, 3123–3127 (1981).

    Article  CAS  Google Scholar 

  18. Fong, I.W. Emerging relations between infectious diseases and coronary artery disease and atherosclerosis. Can. Med. Assoc. J. 163, 49–56 (2000).

    CAS  Google Scholar 

  19. Oka, K. et al. Human very-low-density lipoprotein receptor complementary DNA and deduced amino acid sequence and localization of its gene (VLDLR) to chromosome band 9p24 by fluorescence in situ hybridization. Genomics 20, 298–300 (1994).

    Article  CAS  Google Scholar 

  20. Fernández-Ruiz, E., Armesilla, A.L., Sánchez-Madrid, F. & Vega, M.A. Gene encoding the collagen type I and thrombospondin receptor CD36 is located on chromosome 7q11.2. Genomics 17, 759–761 (1993).

    Article  Google Scholar 

  21. Humbert, R. et al. The molecular basis of the human serum paraoxonase activity polymorphism. Nature Genet. 3, 73–76 (1993).

    Article  CAS  Google Scholar 

  22. Klinger, K.W. et al. Plasminogen activator inhibitor type 1 gene is located at region q21.3–q22 of chromosome 7 and genetically linked with cystic fibrosis. Proc. Natl Acad. Sci. USA 84, 8548–8552 (1987).

    Article  CAS  Google Scholar 

  23. Whitmore, T.E., Day, J.R. & Albers, J.J. Localization of the human phospholipid transfer protein gene to chromosome 20q12–q13.1. Genomics 28, 599–600 (1995).

    Article  CAS  Google Scholar 

  24. Rust, S. et al. Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nature Genet. 22, 352–355 (1999).

    Article  CAS  Google Scholar 

  25. Vionnet, N. et al. Genomewide search for type 2 diabetes–susceptibility genes in French Whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2 diabetes locus on chromosome 1q21–q24. Am. J. Hum. Genet. 67, 1470–1480 (2000).

    Article  CAS  Google Scholar 

  26. Kissebah, A.H. et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc. Natl Acad. Sci. USA 97, 14478–14483 (2000).

    Article  CAS  Google Scholar 

  27. Imperatore, G. et al. A locus influencing total serum cholesterol on chromosome 19p. Arterioscler. Thromb. Vasc. Biol. 20, 2651–2656 (2000).

    Article  CAS  Google Scholar 

  28. Duggirala, R. et al. Linkage of type 2 diabetes mellitus and of age of onset to a genetic location of chromosome 10q in Mexican Americans. Am. J. Hum. Genet. 64, 1127–1140 (1999).

    Article  CAS  Google Scholar 

  29. Duggirala, R. et al. A major susceptibility locus influencing plasma triglyceride concentrations is located on chromosome 15q in Mexican Americans. Am. J. Hum. Genet. 66, 1237–1245 (2000).

    Article  CAS  Google Scholar 

  30. Almasy, L. & Blangero, J. Multipoint quantitative-trait linkage analysis in general pedigrees. Am. J. Hum. Genet. 62, 1198–1211 (1998).

    Article  CAS  Google Scholar 

  31. Self, S.G. & Liang, K-Y. Asymptotic properties of maximum likelihood estimators and likelihood ratio tests under nonstandard conditions. J. Am. Stat. Assoc. 82, 605–610 (1987).

    Article  Google Scholar 

Download references

Acknowledgements

This research was supported by grants from the National Institutes of Health. R.A. was supported by the ADA Mentor-based Postdoctoral Fellowship program. We would like to thank R. Cheruvu, E. Benavides, S. Fleming, M. Zavala and B. Reus for technical assistance. We also wish to thank the participants of the SAFADS families for their support and cooperation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rector Arya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arya, R., Duggirala, R., Almasy, L. et al. Linkage of high-density lipoprotein–cholesterol concentrations to a locus on chromosome 9p in Mexican Americans. Nat Genet 30, 102–105 (2002). https://doi.org/10.1038/ng810

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng810

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing