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Kindt, A. ; Fuerst, R.W. ; Knoop, J. ; Laimighofer, M. ; Telieps, T. ; Hippich, M. ; Woerheide, M.A. ; Wahl, S. ; Wilson, R. ; Sedlmeier, E.-M. ; Hommel, A.* ; Todd, J.A.* ; Krumsiek, J. ; Ziegler, A.-G. ; Bonifacio, E.

Allele-specific methylation of type 1 diabetes susceptibility genes.

J. Autoimmun. 89, 63-74 (2018)
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The susceptibility to autoimmune diseases is influenced by genes encoding major histocompatibility complex (MHC) proteins. By examining the epigenetic methylation maps of cord blood samples, we found marked differences in the methylation status of CpG sites within the MHC genes (cis-metQTLs) between carriers of the type 1 diabetes risk haplotypes HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) and HLA-DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8). These differences were found in children and adults, and were accompanied by reduced HLA-DR protein expression in immune cells with the HLA-DR3-DQ2 haplotype. Extensive cis-metQTLs were identified in all 45 immune and non-immune type 1 diabetes susceptibility genes analyzed in this study. We observed and validated a novel association between the methylation status of CpG sites within the LDHC gene and the development of insulin autoantibodies in early childhood in children who are carriers of the highest type 1 diabetes risk genotype. Functionally relevant epigenetic changes in susceptibility genes may represent therapeutic targets for type 1 diabetes.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Autoimmunity ; Epigenetics ; Hla ; Insulin Autoantibodies ; Insulin Gene ; Lactate Dehydrogenase C
Language
Publication Year 2018
Prepublished in Year 2017
HGF-reported in Year 2017
ISSN (print) / ISBN 0896-8411
e-ISSN 0896-8411
Journal Journal of Autoimmunity
Quellenangaben Volume: 89, Issue: , Pages: 63-74 Article Number: , Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research (IDF)
Institute of Computational Biology (ICB)
Institute of Diabetes and Obesity (IDO)
Institute of Epidemiology (EPI)
POF-Topic(s) 30201 - Metabolic Health
30505 - New Technologies for Biomedical Discoveries
30205 - Bioengineering and Digital Health
90000 - German Center for Diabetes Research
30202 - Environmental Health
Research field(s) Helmholtz Diabetes Center
Enabling and Novel Technologies
Genetics and Epidemiology
PSP Element(s) G-502100-001
G-508600-006
G-554100-001
G-501900-382
G-503800-001
G-501900-229
G-504091-002
G-504091-001
G-501900-402
DOI 10.1016/j.jaut.2017.11.008
WOS ID WOS:000431158100007
Scopus ID 85044711033
PubMed ID 29224923
Erfassungsdatum 2017-12-27
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