Epigenetics of Lipid Phenotypes
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LIPIDS (L. PARNELL & J. ORDOVAS, SECTION EDITORS)
Epigenetics of Lipid Phenotypes Sergi Sayols-Baixeras 1,2 & Marguerite R. Irvin 3 & Roberto Elosua 4 & Donna K. Arnett 1 & Stella W. Aslibekyan 3
# Springer Science+Business Media New York 2016
Abstract Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (eg, CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay between different classes of epigenetic processes in the lipid-related genomic regions. Although epigenetic findings hold the potential to explain the interindividual variability in lipid profiles as well as the underlying mechanisms, they have yet to be translated into effective therapies for dyslipidemia.
Keywords Epigenetics . Methylation . Lipids . Triglycerides . Cholesterol This article is part of the Topical Collection on Lipids * Stella W. Aslibekyan [email protected] 1
College of Public Health, University of Kentucky, Lexington, KY, USA
2
Universitat Pompeu Fabra (UPF), Barcelona, Spain
3
Department of Epidemiology, University of Alabama at Birmingham, 1665 University Blvd, RPHB 230J, Birmingham, AL, USA
4
Cardiovascular Epidemiology and Genetics Group, Institut Hospital del Mar d’Investigacions Mediques (IMIM), Barcelona, Spain
Introduction Elevated plasma triglycerides (TGs), alone or in conjunction with increased low-density lipoprotein (LDL) and decreased high-density lipoprotein (HDL) cholesterol, are welldocumented risk factors for cardiovascular disease [1]. Despite high estimates of heritability (48 % and above [2]) and limited influence of shared environment, known genetic variants explain approximately 10 % of the observed variance in plasma lipids [3, 4]. Recent evidence shows that a significant proportion of the remaining genetic variability may be attributable to epigenetic processes, defined as heritable, nonsequence-dependent changes in gene expression [5]. In contrast to sequence polymorphisms, epigenetic variation is specific, dynamic (and even reversible throughout the life course), and mechanistically diverse. These characteristics both make it a lucrative target and pose translational challenges. For example, the cell and tissue specificity enhances pathophysiologic relevance, but often complicates measurements as probing some organs implicated in lipid metabolism—eg, the liver—is invasive and costly. Although several studies have demonstrated conservation of epigenetic patterns and validated the use of easily accessible tissues such as blood for epi
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