Genetic control of coordinated changes in HDL and LDL size phenotypes

David L. Rainwater, Lisa J. Martin, Anthony G. Comuzzie

    Research output: Contribution to journalArticle

    20 Scopus citations

    Abstract

    We investigated the correlation of high density lipoprotein (HDL) and low density lipoprotein (LDL) particle size distributions in samples from >1100 participants in the San Antonio Family Heart Study. By use of analyses of individual correlations of each HDL fraction with each LDL fraction, we devised new metrics for particle size phenotype, termed ΔHDL and ΔLDL, to optimally reflect the size correlations. Confirming previous studies, we found that the 2 size phenotype variables were positively correlated (r=0.51). Quantitative genetic analysis indicated that nearly half (44%) of the variance in ΔHDL and in ΔLDL was explained by the additive effects of genes. Bivariate genetic analyses indicated that a positive genetic correlation (ρG=0.56) exists between them and suggested that the pleiotropic effects of a gene or group of genes account for ≅31% [ie, ρG2 = (0.56)2=0.31 ] of the genetic variance in the 2 traits. Triglyceride (TG) levels were negatively related to ΔHDL and ΔLDL, with phenotypic correlations of -0.48 and -0.58, respectively, and genetic correlations of -0.45 and -0.76, respectively, suggesting that genes exert significant pleiotropic effects on the covariation of TGs with each of the size variables. Finally, we evaluated a bivariate model for ΔHDL and ΔLDL in which TG level was included as a covariate. This analysis indicated that a small but significant genetic correlation remains for ΔHDL and ΔLDL, even after accounting for the effects of TGs. Thus, our study demonstrates that the phenotypic correlation of HDL and LDL sizes results in part from the pleiotropic actions of a set of genes, some of which also influence TG levels and some of which do not.

    Original languageEnglish (US)
    Pages (from-to)1829-1833
    Number of pages5
    JournalArteriosclerosis, Thrombosis, and Vascular Biology
    Volume21
    Issue number11
    DOIs
    StatePublished - Jan 1 2001

    Keywords

    • Genetics
    • HDL size distributions
    • LDL size distributions
    • Mexican Americans
    • Triglycerides

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

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