Identification of candidate genes encoding an LDL-C QTL in baboons

Genesio M. Karere, Jeremy P. Glenn, Shifra Birnbaum, David L. Rainwater, Michael C. Mahaney, John L. VandeBerg, Laura A. Cox

    Research output: Contribution to journalArticle

    8 Scopus citations

    Abstract

    Cardiovascular disease (CVD) is the leading cause of death in developed countries, and dyslipidemia is a major risk factor for CVD. We previously identified a cluster of quantitative trait loci (QTL) on baboon chromosome 11 for multiple, related quantitative traits for serum LDL-cholesterol (LDL-C). Here we report differentially regulated hepatic genes encoding an LDL-C QTL that influences LDL-C levels in baboons. We performed hepatic whole-genome expression profiling for LDL-C-discordant baboons fed a high-cholesterol, high-fat (HCHF) diet for seven weeks. We detected expression of 117 genes within the QTL 2-LOD support interval. Three genes were differentially expressed in low LDL-C responders and 8 in high LDL-C responders in response to a HCHF diet. Seven genes (ACVR1B, CALCOCO1, DGKA, ERBB3, KRT73, MYL6B, TENC1) showed discordant expression between low and high LDL-C responders. To prioritize candidate genes, we integrated miRNA and mRNA expression profiles using network tools and found that four candidates (ACVR1B, DGKA, ERBB3, TENC1) were miRNA targets and that the miRNAs were inversely expressed to the target genes. Candidate gene expression was validated using QRT-PCR and Western blotting. This study reveals candidate genes that influence variation in LDL-C in baboons and potential genetic mechanisms for further investigation.

    Original languageEnglish (US)
    Pages (from-to)1776-1785
    Number of pages10
    JournalJournal of lipid research
    Volume54
    Issue number7
    DOIs
    StatePublished - Jul 1 2013

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    Keywords

    • Cardiovascular disease
    • Diet-responsive liver gene expression
    • Dyslipidemia
    • Low density lipoprotein-cholesterol

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology
    • Cell Biology

    Cite this

    Karere, G. M., Glenn, J. P., Birnbaum, S., Rainwater, D. L., Mahaney, M. C., VandeBerg, J. L., & Cox, L. A. (2013). Identification of candidate genes encoding an LDL-C QTL in baboons. Journal of lipid research, 54(7), 1776-1785. https://doi.org/10.1194/jlr.M032649