Pleiotropy and genotype by diet interaction in a baboon model for atherosclerosis: A multivariate quantitative genetic analysis of HDL subfractions in two dietary environments

Michael C. Mahaney, John Blangero, David L. Rainwater, Glen E. Mott, Anthony G. Comuzzie, Jean W. MacCluer, John L. VandeBerg

    Research output: Contribution to journalArticle

    31 Scopus citations

    Abstract

    We investigated dietary effects on pleiotropic relationships among 3 HDL cholesterol (C) subfractions (HDL1-C, HDL2-C, and HDL3-C; levels quantified by gradient gel electrophoresis) for 942 pedigreed baboons (Papio hamadryas) who were fed a basal (Chow) diet and a high cholesterol, saturated fat (HCSF) challenge diet. Using multivariate maximum likelihood methods we estimated heritabilities for all 6 traits, genetic and environmental correlations (ρ(G) and ρ(E)) between them, and the additive genetic variance of each subfraction's response to the diets. On the Chow diet, genetic correlations between the 3 subfractions were significant, and we observed complete pleiotropy between HDL1-C and HDL3-C (ρ(G) = -0.81). On the HCSF diet, only the genetic correlation between HDL1-C and HDL3-C (ρ(G)=-0.61) was significant. Genetic correlations between individual subfractions on the Chow and HCSF diets did not differ significantly from 1.0, indicating that the same additive genes influenced each subfraction's levels regardless of diet. However, the additive genetic variance of response to the diets was highly significant for HDL1-C and HDL2-C, but not for HDL3-C. Similar sets of genes influence variation in the 3 HDL subfractions on the Chow diet, and the same set influences variation in each subfraction on the HCSF diet. However, the expression of genes influencing HDL1-C and HDL2-C is altered by the HCSF diet, disrupting the pleiotropy observed between the 3 subfractions on the Chow diet.

    Original languageEnglish (US)
    Pages (from-to)1134-1141
    Number of pages8
    JournalArteriosclerosis, Thrombosis, and Vascular Biology
    Volume19
    Issue number4
    DOIs
    StatePublished - Apr 1999

      Fingerprint

    Keywords

    • Animal models
    • Atherosclerosis risk factors
    • Dietary challenge
    • Gradient gel electrophoresis
    • Lipemic response
    • Statistical genetics

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

    Cite this