Two major loci control variation in β-lipoprotein cholesterol and response to dietary fat and cholesterol in Baboons

David L. Rainwater, Candace M. Kammerer, James E. Hixson, K. D. Carey, Karen S. Rice, Bennett Dyke, Jane F. VandeBerg, Susan H. Slifer, Larry D. Atwood, Henry C. McGill, John L. VandeBerg

    Research output: Contribution to journalArticle

    17 Scopus citations

    Abstract

    We explored the genetic Control of cholesterolemic responses to dietary cholesterol and fat in 575 pedigreed baboons. We measured cholesterol in β- lipoproteins (low density lipoprotein cholesterol [LDLC]) in blood drawn from baboons while they were consuming a baseline (low in cholesterol and fat) diet, a high-saturated fat (lard) diet, and a high-cholesterol, high- saturated fat diet. In addition to baseline levels (LDLC(Base)), we analyzed two variables for diet response: LDLC(RF), which represents the LDLC response to increasing dietary fat (ie, high-fat diet minus baseline), and LDLC(RC), which represents the LDLC response to increasing dietary Cholesterol level (ie, high-cholesterol, high-fat diet minus high-fat diet). Heritabilities (h2) of the 3 traits were 0.59 for LDLC(Base), 0.14 for LDLC(RF), and 0.59 for LDLC(RC). In addition, LDLC(Base) and LDLC(RC) had a significant genetic correlation (ie; ρ(G) = 0.54), suggesting that 1 or more genes exert pleiotropic effects on the 2 traits. Segregation analyses detected a single major locus that accounted for nearly all genetic variation in LDLC(RC) and some genetic variation in LDLC(Base) and LDLC(RF) and confirmed the presence of a different major locus that influences LDLC(Base) alone. Preliminary linkage analyses indicated that neither locus was linked to the LDL receptor gene, a likely candidate locus for LDLC. Detection of these major loci with large effects on the LDLC response to dietary cholesterol in a nonhuman primate offers hope of detecting and ultimately identifying similar loci that determine LDLC variation in human populations.

    Original languageEnglish (US)
    Pages (from-to)1061-1068
    Number of pages8
    JournalArteriosclerosis, Thrombosis, and Vascular Biology
    Volume18
    Issue number7
    DOIs
    StatePublished - Jan 1 1998

    Keywords

    • Baboons
    • Diet
    • Genetics
    • LDL

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

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  • Cite this

    Rainwater, D. L., Kammerer, C. M., Hixson, J. E., Carey, K. D., Rice, K. S., Dyke, B., VandeBerg, J. F., Slifer, S. H., Atwood, L. D., McGill, H. C., & VandeBerg, J. L. (1998). Two major loci control variation in β-lipoprotein cholesterol and response to dietary fat and cholesterol in Baboons. Arteriosclerosis, Thrombosis, and Vascular Biology, 18(7), 1061-1068. https://doi.org/10.1161/01.ATV.18.7.1061