Allele-specific methylation of type 1 diabetes susceptibility genes

被引：27
|
作者：
Kindt, Alida S. D. [1 ]
Fuerst, Rainer W. [2 ]
Knoop, Jan [2 ]
Laimighofer, Michael [1 ]
Telieps, Tanja [3 ]
Hippich, Markus [2 ]
Woerheide, Maria A. [1 ]
Wahl, Simone [4 ,5 ,6 ]
Wilson, Rory [4 ,5 ]
Sedlmeier, Eva-Maria [2 ]
Hommel, Angela [7 ]
Todd, John A. [8 ]
Krumsiek, Jan [1 ,6 ]
Ziegler, Anette-G. [2 ,9 ]
Bonifacio, Ezio [3 ,7 ,9 ]
机构：
[1] Helmholtz Zentrum Munchen, Inst Computat Biol, Neuherberg, Germany
[2] Helmholtz Zentrum Munchen, Inst Diabet Res, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany
[3] Helmholtz Zentrum Munchen, Inst Diabet & Obes, Neuherberg, Germany
[4] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany
[5] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany
[6] German Ctr Diabet Res DZD, Neuherberg, Germany
[7] Tech Univ, Fac Med Carl Gustav Carus, Ctr Regenerat Therapies Dresden, Dresden, Germany
[8] Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, JDRF Wellanne Trust Diabet & Inflammat Lab, Oxford, England
[9] Forschergrp Diabet eV, Neuherberg, Germany
来源：
JOURNAL OF AUTOIMMUNITY | 2018年 / 89卷
关键词：
Epigenetics; Autoimmunity; HLA; Insulin autoantibodies; Insulin gene; Lactate dehydrogenase C; ALPHA-BETA-HETERODIMER; HLA-DQ ALLELES; CLASS-II GENES; CELIAC-DISEASE; DNA METHYLATION; ISLET AUTOANTIBODIES; IMMUNE-RESPONSES; WIDE ASSOCIATION; GERMAN BABYDIAB; RISK;
D O I：
10.1016/j.jaut.2017.11.008
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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 HIA-DR protein expression in immune cells with the EILA-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. (C) 2017 The Authors. Published by Elsevier Ltd.
引用
收藏
页码：63 / 74
页数：12
相关论文
共 50 条
  • [21] DAMEfinder: a method to detect differential allele-specific methylation
    Orjuela, Stephany
    Machlab, Dania
    Menigatti, Mirco
    Marra, Giancarlo
    Robinson, Mark D.
    EPIGENETICS & CHROMATIN, 2020, 13 (01)
  • [22] Allele-specific silencing of dominant disease genes
    Miller, VM
    Xia, HB
    Marrs, GL
    Gouvion, CM
    Lee, G
    Davidson, BL
    Paulson, HL
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (12) : 7195 - 7200
  • [23] Allele-specific methylation of the NF1 gene during development.
    Haines, TR
    Rodenhiser, DR
    Ainsworth, PJ
    AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 69 (04) : 266 - 266
  • [24] Allele-specific DNA methylation reinforces PEAR1 enhancer activity
    Izzi, Benedetta
    Pistoni, Mariaelena
    Cludts, Katrien
    Akkor, Pinar
    Lambrechts, Diether
    Verfaillie, Catherine
    Verhamme, Peter
    Freson, Kathleen
    Hoylaerts, Marc F.
    BLOOD, 2016, 128 (07) : 1003 - 1012
  • [25] ALLELE-SPECIFIC METHYLATION OF THE HUMAN C-HA-RAS-1 GENE
    CHANDLER, LA
    GHAZI, H
    JONES, PA
    BOUKAMP, P
    FUSENIG, NE
    CELL, 1987, 50 (05) : 711 - 717
  • [26] Allele-specific transcriptional regulation of HLA-DQB1 genes
    Nepom, GT
    Sukiennicki, T
    Beaty, JS
    HUMAN IMMUNOLOGY, 1996, 47 (1-2) : O43 - O43
  • [27] Identifying the lungs as a susceptible site for allele-specific regulatory changes associated with type 1 diabetes risk
    Ho, Daniel
    Nyaga, Denis M.
    Schierding, William
    Saffery, Richard
    Perry, Jo K.
    Taylor, John A.
    Vickers, Mark H.
    Kempa-Liehr, Andreas W.
    O'Sullivan, Justin M.
    COMMUNICATIONS BIOLOGY, 2021, 4 (01)
  • [28] Identifying the lungs as a susceptible site for allele-specific regulatory changes associated with type 1 diabetes risk
    Daniel Ho
    Denis M. Nyaga
    William Schierding
    Richard Saffery
    Jo K. Perry
    John A. Taylor
    Mark H. Vickers
    Andreas W. Kempa-Liehr
    Justin M. O’Sullivan
    Communications Biology, 4
  • [29] Characterization and machine learning prediction of allele-specific DNA methylation
    He, Jianlin
    Sun, Ming-an
    Wang, Zhong
    Wang, Qianfei
    Li, Qing
    Xie, Hehuang
    GENOMICS, 2015, 106 (06) : 331 - 339
  • [30] Profiling total and allele-specific DNA methylation in human placentas
    Kerkel, K.
    Jiang, L.
    Yuan, E.
    Spadola, A.
    Morris, M.
    Haghighi, V.
    Tycko, B.
    PLACENTA, 2007, 28 (8-9) : A7 - A7
12345