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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)
Verlagsversion Postprint DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Autoimmunity ; Epigenetics ; Hla ; Insulin Autoantibodies ; Insulin Gene ; Lactate Dehydrogenase C
ISSN (print) / ISBN 0896-8411
e-ISSN 0896-8411
Zeitschrift Journal of Autoimmunity
Quellenangaben Band: 89, Heft: , Seiten: 63-74 Artikelnummer: , Supplement: ,
Verlag Elsevier
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research Type 1 (IDF)
Institute of Computational Biology (ICB)
Institute of Diabetes and Obesity (IDO)
Institute of Epidemiology II (EPI2)