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Pfeiffer, L. ; Wahl, S. ; Pilling, L.C.* ; Reischl, E. ; Sandling, J.K.* ; Kunze, S. ; Holdt, L.M.* ; Kretschmer, A. ; Schramm, K. ; Adamski, J. ; Klopp, N.* ; Illig, T.* ; Hedman, A.K.* ; Roden, M.* ; Hernandez, D.G.* ; Singleton, A.B.* ; Thasler, W.E.* ; Grallert, H. ; Gieger, C. ; Herder, C.* ; Teupser, D.* ; Meisinger, C. ; Spector, T.D.* ; Kronenberg, F.* ; Prokisch, H. ; Melzer, D.* ; Peters, A. ; Deloukas, P.* ; Ferrucci, L.* ; Waldenberger, M.

DNA methylation of lipid-related genes affects blood lipid levels.

Circ. Cardiovasc. Genet. 8, 334-342 (2015)
Verlagsversion DOI PMC
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 (beta coefficient=-0.049; P=8.26E-17) and triglyceride levels (beta=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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Abcg1 ; Ewas ; Illumina 450k ; Epidemiology ; Epigenetics ; Expression ; Gene Expression ; Genetic Epidemiology ; Lipids And Lipoproteins ; Myocardial Infarction; Binding Cassette Transporter; Epigenome-wide Association; Coronary-artery-disease; Foam-cell-formation; Cholesterol Homeostasis; Quantile Normalization; Lowering Drugs; Heart-disease; Diet Network; Ppar-alpha
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 1942-325X
e-ISSN 1942-3268
Zeitschrift Circulation: Cardiovascular Genetics
Quellenangaben Band: 8, Heft: 2, Seiten: 334-342 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Hagerstown, Md
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Genetic Epidemiology (IGE)
POF Topic(s) 30202 - Environmental Health
90000 - German Center for Diabetes Research
30201 - Metabolic Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504091-001
G-504091-002
G-504091-004
G-504000-006
G-501900-071
G-505600-001
G-500700-001
G-501900-401
G-501900-402
G-504100-001
PubMed ID 25583993
DOI 10.1161/CIRCGENETICS.114.000804
WOS ID WOS:000353309600012
Scopus ID 84942908108
Erfassungsdatum 2015-05-15
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