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Linkage analysis of the genetic determinants of high density lipoprotein concentrations and composition: evidence for involvement of the apolipoprotein A-II and cholesteryl ester transfer protein loci

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Abstract

We have tested for evidence of linkage between the genetic loci determining concentrations and composition of plasma high density lipoproteins (HDL) with the genes for the major apolipoproteins and enzymes participating in lipoprotein metabolism. These genes include those encoding various apolipoproteins (apo), including apoA-I, apoA-II, apoA-IV, apoB, apoC-I, apoC-II, apoC-III, apoE, and apo(a), cholesteryl ester transfer protein (CETP), HDL-binding protein, lipoprotein lipase, and the low density lipoprotein (LDL) receptor. Polymorphisms of these genes, and nearby highly polymorphic simple sequence repeat markers, were examined by quantitative sib-pair linkage analysis in 30 coronary artery disease families consisting of a total of 366 individuals. Evidence for linkage was observed between a marker locus D16S313 linked to the CETP locus and a locus determining plasma HDL-cholesterol concentration (P = 0.002), and the genetic locus for apoA-II and a locus determining the levels of the major apolipoproteins of HDL, apoA-I and apoA-II (P = 0.009 and 0.02, respectively). HDL level was also influenced by the variation at the apo(a) locus on chromosome 6 (P = 0.02). Thus, these data indicate the simultaneous involvement of at least two different genetic loci in the determination of the levels of HDL and its associated lipoproteins.

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Authors and Affiliations

  1. Divisions of Medical Genetics and Cardiology, Departments of Medicine and Pediatrics, Cedars-Sinai Medical Center, 90048, Los Angeles, CA, USA

    Xiangdong Bu, Jane Brown, Richard J. Gray & Jerome I. Rotter

  2. Departments of Medicine and Microbiology and Molecular Genetics, and Molecular Biology Institute, University of California, 90024, Los Angeles, CA, USA

    Craig H. Warden, Yu-Rong Xia, Cynthia De Meester, Scott Teruya, Beth Lokensgard, Siamac Daneshmand & Aldons J. Lusis

  3. Department of Chemistry and Biochemistry, University of California, 90024, Los Angeles, CA, USA

    Donald L. Puppione

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  1. Xiangdong Bu
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  2. Craig H. Warden
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  3. Yu-Rong Xia
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Bu, X., Warden, C.H., Xia, YR. et al. Linkage analysis of the genetic determinants of high density lipoprotein concentrations and composition: evidence for involvement of the apolipoprotein A-II and cholesteryl ester transfer protein loci. Hum Genet 93, 639–648 (1994). https://doi.org/10.1007/BF00201563

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  • DOI: https://doi.org/10.1007/BF00201563

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