DNA Methylation of Lipid-Related Genes Affects Blood Lipid Levels

被引：151

作者：

Pfeiffer, Liliane ^{[1
,2
]}

Wahl, Simone ^{[1
,2
,6
]}

Pilling, Luke C. ^{[7
]}

Reischl, Eva ^{[1
,2
]}

Sandling, Johanna K. ^{[8
]}

Kunze, Sonja ^{[1
,2
]}

Holdt, Lesca M. ^{[9
,10
]}

Kretschmer, Anja ^{[1
,2
,11
]}

Schramm, Katharina ^{[3
,12
]}

Adamski, Jerzy ^{[4
]}

Klopp, Norman ^{[13
]}

Illig, Thomas ^{[13
]}

Hedman, Asa K. ^{[14
]}

Roden, Michael ^{[15
,16
,17
]}

Hernandez, Dena G. ^{[18
]}

Singleton, Andrew B. ^{[18
]}

Thasler, Wolfgang E. ^{[19
]}

Grallert, Harald ^{[1
,2
,6
]}

Gieger, Christian ^{[5
]}

Herder, Christian ^{[15
,16
]}

Teupser, Daniel ^{[9
,10
]}

Meisinger, Christa ^{[2
]}

Spector, Timothy D. ^{[20
]}

Kronenberg, Florian ^{[21
]}

Prokisch, Holger ^{[3
,12
]}

Melzer, David ^{[7
]}

Peters, Annette ^{[1
,2
,22
]}

Deloukas, Panos ^{[8
,23
,24
]}

Ferrucci, Luigi ^{[25
]}

Waldenberger, Melanie ^{[1
,2
]}

机构：

[1] Res Unit Mol Epidemiol, Neuherberg, Germany

[2] Inst Epidemiol 2, Neuherberg, Germany

[3] Inst Human Genet, Neuherberg, Germany

[4] Inst Expt Genet, Genome Anal Ctr, Neuherberg, Germany

[5] German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany

[6] German Ctr Diabet Res DZD, Neuherberg, Germany

[7] Univ Exeter, Sch Med, Epidemiol & Publ Hlth Grp, Exeter, Devon, England

[8] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Hinxton, Cambs, England

[9] Univ Hosp Munich, Inst Lab Med, Munich, Germany

[10] Univ Munich, Munich, Germany

[11] Univ Kiel, Dept Dermatol Venereol & Allergy, Kiel, Germany

[12] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany

[13] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany

[14] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[15] German Ctr Diabet Res DZD, Dusseldorf, Germany

[16] Univ Dusseldorf, Inst Clin Diabetol, German Diabet Ctr, Leibniz Ctr Diabet Res, Dusseldorf, Germany

[17] Univ Hosp, Dept Endocrinol & Diabetol, Dusseldorf, Germany

[18] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

[19] Hosp Univ Munich, Biobank Adm HTCR, Dept Gen Visceral Transplantat Vasc & Thorac Surg, Munich, Germany

[20] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

[21] Med Univ Innsbruck, Div Genet Epidemiol, Dept Med Genet Mol & Clin Pharmacol, A-6020 Innsbruck, Austria

[22] Partner Site Munich, German Res Ctr Cardiovasc Dis DZHK, Munich, Germany

[23] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England

[24] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21413, Saudi Arabia

[25] NIA, Clin Res Branch, Baltimore, MD 21224 USA

来源：

CIRCULATION-CARDIOVASCULAR GENETICS | 2015年 / 8卷 / 02期

基金：

英国惠康基金;

关键词：

ABCG1; DNA methylatio; epidemiology; gene expression; myocardial infarction; BINDING CASSETTE TRANSPORTER; EPIGENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; QUANTILE NORMALIZATION; CHOLESTEROL EXPORT; LOWERING DRUGS; PPAR-ALPHA; ABCG1; G1; EXPRESSION;

D O I：

10.1161/CIRCGENETICS.114.000804

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：334 / +

页数：43

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