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.
Highlights
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
Nonfasting measurements incorporate those of chylomicrons (CMs) produced in response to dietary fat Abbreviations: CD36, cluster of differentiation 36; CM, chylomicron; CpG, cytosine phosphate guanine; eQTL, expression quantitative trait loci; GOLDN, Genetics of Lipid Lowering Drugs and Diet Network; Linkage disequilibrium (LD), linkage disequilibrium; MAF, minor allele frequency; MetS, metabolic syndrome; MuTHER, Multiple Tissue Human Expression Resource
To determine the potential functional relevance of the lipid-associated SNPs, we examined their influence on CD36 level in adipose and heart, tissues that are highly active in lipid metabolism and where CD36 is abundant. eQTL were available for adipose tissue from 776 healthy individuals of the MuTHER project [38]
Summary
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. 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. Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36. Similar and independent associations were found with levels of nonfasting or postprandial lipids [1, 2] Nonfasting measurements incorporate those of chylomicrons (CMs) produced in response to dietary fat Abbreviations: CD36, cluster of differentiation 36; CM, chylomicron; CpG, cytosine phosphate guanine; eQTL, expression quantitative trait loci; GOLDN, Genetics of Lipid Lowering Drugs and Diet Network; LD, linkage disequilibrium; MAF, minor allele frequency; MetS, metabolic syndrome; MuTHER, Multiple Tissue Human Expression Resource
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
