Determinants of variation in serum paraoxonase enzyme activity in baboons

David L. Rainwater, Michael C. Mahaney, Xing Li Wang, Jeffrey Rogers, Laura A. Cox, John L. Vandeberg

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    19 Scopus citations

    Abstract

    Paraoxonase (PON), an HDL-associated enzyme, is one of many circulating antioxidants thought to play a vital protective role. To better understand the determinants of quantitative variation in serum PON activity, we assayed PON in samples from 611 pedigreed baboons fed three diets. PON was measured enzymatically; the main determinant of variation was genetic and consisted of at least three components: two loci detected by linkage analyses and a residual polygenic component. Multipoint linkage analyses gave peak log of the odds (LOD) scores on the baboon homolog of human chromosome 7q21-22 (near PON1, the structural gene) of 9.1 on the low-cholesterol, high-fat diet and 4.1 on the high-cholesterol, high-fat diet (genome-wide P values were 1 × 10 -8 and 0.0018, respectively). Surprisingly, a second locus on the baboon homolog of human chromosome 12q13 gave a LOD score of 2.9 on the high-cholesterol, high-fat diet (genome-wide P value was 0.032). We identified several significant covariates, including age, sex, diet, and apolipoprotein A-I concentrations. We estimate that 53% of total trait variation in baboons is explained by genes and 17% by covariates, thus accounting for ∼70% of total variation in baboon PON. Although the generation of free radicals is influenced primarily by environmental factors, our findings suggest strong genetic regulation of one component in the antioxidant defense system that plays a major role in susceptibility to atherosclerosis.

    Original languageEnglish (US)
    Pages (from-to)1450-1456
    Number of pages7
    JournalJournal of lipid research
    Volume46
    Issue number7
    DOIs
    StatePublished - Dec 1 2005

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    Keywords

    • Genetic
    • Linkage analysis
    • PON1

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology
    • Cell Biology

    Cite this

    Rainwater, D. L., Mahaney, M. C., Wang, X. L., Rogers, J., Cox, L. A., & Vandeberg, J. L. (2005). Determinants of variation in serum paraoxonase enzyme activity in baboons. Journal of lipid research, 46(7), 1450-1456. https://doi.org/10.1194/jlr.M400473-JLR200