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

7 Citations (Scopus)

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 2013
Externally publishedYes

Fingerprint

Gene encoding
Papio
Quantitative Trait Loci
Genetic Association Studies
LDL Cholesterol
Genes
MicroRNAs
High Fat Diet
Nutrition
Cardiovascular Diseases
Fats
Cholesterol
Chromosomes, Human, Pair 11
Liver
Chromosomes
Dyslipidemias
Developed Countries
Gene expression
Cause of Death
Western Blotting

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

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

Identification of candidate genes encoding an LDL-C QTL in baboons. / Karere, Genesio M.; Glenn, Jeremy P.; Birnbaum, Shifra; Rainwater, David L.; Mahaney, Michael C.; VandeBerg, John L.; Cox, Laura A.

In: Journal of Lipid Research, Vol. 54, No. 7, 07.2013, p. 1776-1785.

Research output: Contribution to journalArticle

Karere, GM, Glenn, JP, Birnbaum, S, Rainwater, DL, Mahaney, MC, VandeBerg, JL & Cox, LA 2013, 'Identification of candidate genes encoding an LDL-C QTL in baboons', Journal of Lipid Research, vol. 54, no. 7, pp. 1776-1785. https://doi.org/10.1194/jlr.M032649
Karere GM, Glenn JP, Birnbaum S, Rainwater DL, Mahaney MC, VandeBerg JL et al. Identification of candidate genes encoding an LDL-C QTL in baboons. Journal of Lipid Research. 2013 Jul;54(7):1776-1785. https://doi.org/10.1194/jlr.M032649
Karere, Genesio M. ; Glenn, Jeremy P. ; Birnbaum, Shifra ; Rainwater, David L. ; Mahaney, Michael C. ; VandeBerg, John L. ; Cox, Laura A. / Identification of candidate genes encoding an LDL-C QTL in baboons. In: Journal of Lipid Research. 2013 ; Vol. 54, No. 7. pp. 1776-1785.
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