title: DNA methylation of lipid-related genes affects blood lipid levels.
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.
  
  
  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.
authors.forename: Liliane
authors.initials: L
authors.lastname: Pfeiffer
authors.forename: Simone
authors.initials: S
authors.lastname: Wahl
authors.forename: Luke C
authors.initials: LC
authors.lastname: Pilling
authors.forename: Eva
authors.initials: E
authors.lastname: Reischl
authors.forename: Johanna K
authors.initials: JK
authors.lastname: Sandling
authors.forename: Sonja
authors.initials: S
authors.lastname: Kunze
authors.forename: Lesca M
authors.initials: LM
authors.lastname: Holdt
authors.forename: Anja
authors.initials: A
authors.lastname: Kretschmer
authors.forename: Katharina
authors.initials: K
authors.lastname: Schramm
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Åsa K
authors.initials: ÅK
authors.lastname: Hedman
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.forename: Dena G
authors.initials: DG
authors.lastname: Hernandez
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Thasler
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.forename: Christa
authors.initials: C
authors.lastname: Meisinger
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.forename: David
authors.initials: D
authors.lastname: Melzer
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D056426:Genetic Loci; D005858:Germany; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D008055:Lipids; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1
keywords: ABCG1; DNA methylatio; epidemiology; gene expression; myocardial infarction