Postprandial lipemia (PPL), the increased plasma TG concentration after consuming a high-fat meal, is an independent risk factor for CVD. Individual responses to a meal high in fat vary greatly, depending on genetic and lifestyle factors. However, only a few loci have been associated with TG-PPL response. Heritable epigenomic changes may be significant contributors to the unexplained inter-individual PPL variability. We conducted an epigenome-wide association study on 979 subjects with DNA methylation measured from CD4+ T cells, who were challenged with a high-fat meal as a part of the Genetics of Lipid Lowering Drugs and Diet Network study. Eight methylation sites encompassing five genes, LPP, CPT1A, APOA5, SREBF1, and ABCG1, were significantly associated with PPL response at an epigenome-wide level (P < 1.1 ∼ 10-7), but no methylation site reached epigenomewide significance after adjusting for baseline TG levels. Higher methylation at LPP, APOA5, SREBF1, and ABCG1, and lower methylation at CPT1A methylation were correlated with an increased TG-PPL response. These PPL-associated methylation sites, also correlated with fasting TG, account for a substantially greater amount of phenotypic variance (14.9%) in PPL and fasting TG (16.3%) when compared with the genetic contribution of loci identified by our previous genomewide association study (4.5%). In summary, the epigenome is a large contributor to the variation in PPL, and this has the potential to be used to modulate PPL and reduce CVD..
|Number of pages||8|
|Journal||Journal of Lipid Research|
|State||Published - 2016|
Bibliographical noteFunding Information:
This work was funded by the U.S. Department of Agriculture under agreement number 8050-51000-098-00D and by National Heart, Lung, and Blood Institute Grant U01-HL072524-04. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the US Department of Agriculture. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture. The USDA is an equal opportunity provider and employer.
Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.
- DNA methylation
- Diet and dietary lipids
- Dietary fat
- Postprandial lipemia
ASJC Scopus subject areas
- Cell Biology