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

Nature Genetics volume 30, pages 102105 (2002) | Download Citation

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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.

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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

Affiliations

  1. Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.

    • Rector Arya
    • , Ravindranath Duggirala
    • , Ken Williams
    •  & Michael P. Stern
  2. Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas, USA.

    • Laura Almasy
    • , David L. Rainwater
    • , Michael C. Mahaney
    • , Shelley Cole
    • , Thomas D. Dyer
    • , Jean W. MacCluer
    •  & John Blangero
  3. Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, USA.

    • Robin J. Leach
  4. Human Genetics Center, UT Houston Health Science Center, Houston, Texas, USA.

    • James E. Hixson
  5. Baylor College of Medicine, Baylor Breast Center, One Baylor Plaza, MS600, Houston, Texas, USA.

    • Peter O'Connell

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Correspondence to Rector Arya.

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DOI

https://doi.org/10.1038/ng810

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