Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

Latisha Love-Gregory, Aldi T. Kraja, Fiona Allum, Stella Aslibekyan, Åsa K. Hedman, Yanan Duan, Ingrid B. Borecki, Donna K. Arnett, Mark I. McCarthy, Panos Deloukas, Jose M. Ordovas, Paul N. Hopkins, Elin Grundberg, Nada A. Abumrad

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Cluster of differentiation 36 (CD36) variants influence fasting lipids and risk of metabolic syndrome, but their impact on postprandial lipids, an independent risk factor for cardiovascular disease, is unclear. We determined the effects of SNPs within a ∼410 kb region encompassing CD36 and its proximal and distal promoters on chylomicron (CM) remnants and LDL particles at fasting and at 3.5 and 6 h following a high-fat meal (Genetics of Lipid Lowering Drugs and Diet Network study, n = 1,117). Five promoter variants associated with CMs, four with delayed TG clearance and five with LDL particle number. To assess mechanisms underlying the associations, we queried expression quantitative trait loci, DNA methylation, and ChIP-seq datasets for adipose and heart tissues that function in postprandial lipid clearance. Several SNPs that associated with higher serum lipids correlated with lower adipose and heart CD36 mRNA and aligned to active motifs for PPARγ, a major CD36 regulator. The SNPs also associated with DNA methylation sites that related to reduced CD36 mRNA and higher serum lipids, but mixed-model analyses indicated that the SNPs and methylation independently influence CD36 mRNA. The findings support contributions of CD36 SNPs that reduce adipose and heart CD36 RNA expression to inter-individual variability of postprandial lipid metabolism and document changes in CD36 DNA methylation that influence both CD36 expression and lipids.

Original languageEnglish
Pages (from-to)2176-2184
Number of pages9
JournalJournal of lipid research
Volume57
Issue number12
DOIs
StatePublished - 2016

Keywords

  • Cholesterol/metabolism
  • Cluster of differentiation 36
  • Deoxyribonucleic acid
  • Dietary lipids
  • Dyslipidemia
  • Genetics
  • Lipoproteins
  • Low density lipoprotein
  • Single nucleotide polymorphism

Fingerprint

Dive into the research topics of 'Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36'. Together they form a unique fingerprint.

Cite this