| Literature DB >> 29224923 |
Alida S D Kindt1, Rainer W Fuerst2, Jan Knoop3, Michael Laimighofer4, Tanja Telieps5, Markus Hippich6, Maria A Woerheide7, Simone Wahl8, Rory Wilson9, Eva-Maria Sedlmeier10, Angela Hommel11, John A Todd12, Jan Krumsiek13, Anette-G Ziegler14, Ezio Bonifacio15.
Abstract
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.Entities:
Keywords: Autoimmunity; Epigenetics; HLA; Insulin autoantibodies; Insulin gene; Lactate dehydrogenase C
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Year: 2017 PMID： 29224923 DOI： 10.1016/j.jaut.2017.11.008
Source DB: PubMed Journal: J Autoimmun ISSN： 0896-8411 Impact factor: 7.094