1. DNA methylation of lipid-related genes affects blood lipid levels
- Author
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Dena G. Hernandez, Lesca M. Holdt, Åsa K. Hedman, Christian Herder, Thomas Illig, Andrew B. Singleton, Christa Meisinger, Luigi Ferrucci, Liliane Pfeiffer, Johanna K. Sandling, Katharina Schramm, Harald Grallert, David Melzer, Anja Kretschmer, Luke C. Pilling, Christian Gieger, Holger Prokisch, Wolfgang E. Thasler, Michael Roden, N. Klopp, Florian Kronenberg, Jerzy Adamski, Tim D. Spector, Sonja Kunze, Panos Deloukas, Simone Wahl, Annette Peters, Melanie Waldenberger, Eva Reischl, and Daniel Teupser more...
- Subjects
Adult ,Male ,medicine.medical_specialty ,Myocardial Infarction ,Blood lipids ,Adipose tissue ,Biology ,Bioinformatics ,Article ,Epigenesis, Genetic ,Cohort Studies ,chemistry.chemical_compound ,Internal medicine ,Germany ,Genetics ,medicine ,Humans ,Abcg1 ,Ewas ,Illumina 450k ,Epidemiology ,Epigenetics ,Expression ,Gene Expression ,Genetic Epidemiology ,Lipids And Lipoproteins ,Genetics (clinical) ,Whole blood ,ATP Binding Cassette Transporter, Subfamily G, Member 1 ,Aged ,Aged, 80 and over ,Triglyceride ,Methylation ,DNA Methylation ,Middle Aged ,Lipids ,Endocrinology ,chemistry ,CpG site ,Genetic Loci ,DNA methylation ,lipids (amino acids, peptides, and proteins) ,ATP-Binding Cassette Transporters ,Female ,Cardiology and Cardiovascular Medicine ,Sterol Regulatory Element Binding Protein 1 - Abstract
Background— Epigenetic mechanisms might be involved in the regulation of interindividual lipid level variability and thus may contribute to the cardiovascular risk profile. The aim of this study was to investigate the association between genome-wide DNA methylation and blood lipid levels high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. Observed DNA methylation changes were also further analyzed to examine their relationship with previous hospitalized myocardial infarction. Methods and Results— Genome-wide DNA methylation patterns were determined in whole blood samples of 1776 subjects of the Cooperative Health Research in the Region of Augsburg F4 cohort using the Infinium HumanMethylation450 BeadChip (Illumina). Ten novel lipid-related CpG sites annotated to various genes including ABCG1 , MIR33B/SREBF1 , and TNIP1 were identified. CpG cg06500161, located in ABCG1 , was associated in opposite directions with both high-density lipoprotein cholesterol (β coefficient=−0.049; P =8.26E-17) and triglyceride levels (β=0.070; P =1.21E-27). Eight associations were confirmed by replication in the Cooperative Health Research in the Region of Augsburg F3 study (n=499) and in the Invecchiare in Chianti, Aging in the Chianti Area study (n=472). Associations between triglyceride levels and SREBF1 and ABCG1 were also found in adipose tissue of the Multiple Tissue Human Expression Resource cohort (n=634). Expression analysis revealed an association between ABCG1 methylation and lipid levels that might be partly mediated by ABCG1 expression. DNA methylation of ABCG1 might also play a role in previous hospitalized myocardial infarction (odds ratio, 1.15; 95% confidence interval=1.06–1.25). Conclusions— Epigenetic modifications of the newly identified loci might regulate disturbed blood lipid levels and thus contribute to the development of complex lipid-related diseases. more...
- Published
- 2014