DNA Methylation of Lipid-Related Genes Affects Blood Lipid Levels

Liliane Pfeiffer, Simone Wahl, Luke C. Pilling, Eva Reischl, Johanna K. Sandling, Sonja Kunze, Lesca M. Holdt, Anja Kretschmer, Katharina Schramm, Jerzy Adamski, Norman Klopp, Thomas Illig, Åsa K. Hedman, Michael Roden, Dena G. Hernandez, Andrew B. Singleton, Wolfgang E. Thasler, Harald Grallert, Christian Gieger, Christian HerderDaniel Teupser, Christa Meisinger, Timothy D. Spector, Florian Kronenberg, Holger Prokisch, David Melzer, Annette Peters, Panos Deloukas, Luigi Ferrucci, Melanie Waldenberger

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)334-342
Number of pages9
JournalCirculation: Cardiovascular Genetics
Volume8
Issue number2
DOIs
StatePublished - Apr 4 2015
Externally publishedYes

Keywords

  • ABCG1
  • DNA methylatio
  • epidemiology
  • gene expression
  • myocardial infarction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)
  • Genetics
  • Medicine(all)

Fingerprint Dive into the research topics of 'DNA Methylation of Lipid-Related Genes Affects Blood Lipid Levels'. Together they form a unique fingerprint.

  • Cite this

    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, Å. K., Roden, M., Hernandez, D. G., Singleton, A. B., Thasler, W. E., Grallert, H., Gieger, C., ... Waldenberger, M. (2015). DNA Methylation of Lipid-Related Genes Affects Blood Lipid Levels. Circulation: Cardiovascular Genetics, 8(2), 334-342. https://doi.org/10.1161/CIRCGENETICS.114.000804