Hypomethylation within gene promoter regions and type 1 diabetes in discordant monozygotic twins

Journal of Autoimmunity
Emon ElboudwarejJanelle A Noble

Abstract

Genetic susceptibility to type 1 diabetes (T1D) is well supported by epidemiologic evidence; however, disease risk cannot be entirely explained by established genetic variants identified so far. This study addresses the question of whether epigenetic modification of the inherited DNA sequence may contribute to T1D susceptibility. Using the Infinium HumanMethylation450 BeadChip array (450k), a total of seven long-term disease-discordant monozygotic (MZ) twin pairs and five pairs of HLA-identical, disease-discordant non-twin siblings (NTS) were examined for associations between DNA methylation (DNAm) and T1D. Strong evidence for global hypomethylation of CpG sites within promoter regions in MZ twins with TID compared to twins without T1D was observed. DNA methylation data were then grouped into three categories of CpG sites for further analysis, including those within: 1) the major histocompatibility complex (MHC) region, 2) non-MHC genes with reported T1D association through genome wide association studies (GWAS), and 3) the epigenome, or remainder of sites that did not include MHC and T1D associated genes. Initial results showed modest methylation differences between discordant MZ twins for the MHC region and T1D-associated CpG...Continue Reading

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Citations

Apr 8, 2016·Clinical Reviews in Allergy & Immunology·Yin ZhouQianjin Lu
Apr 13, 2017·Pediatric Diabetes·Amita Bansal, Sara E Pinney
Jul 29, 2017·World Journal of Diabetes·Giuseppe Galvani, Georgia Fousteri
Dec 22, 2019·International Journal of Molecular Sciences·Marie Cerna
Jul 6, 2018·Cellular and Molecular Life Sciences : CMLS·Zijun WangQianjin Lu
Nov 24, 2016·Clinical Reviews in Allergy & Immunology·Zhen WangZhiguang Zhou
Sep 27, 2019·Frontiers in Endocrinology·Susanna EspositoNicola Principi
Sep 10, 2019·Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies·Paul N Baird, Pirro Hysi
Oct 3, 2020·International Journal of Molecular Sciences·Valérie Gagné-OuelletLuigi Bouchard
Nov 13, 2020·Frontiers in Cell and Developmental Biology·Laura J SmythAmy Jayne McKnight
May 25, 2021·Frontiers in Endocrinology·Nazia Parveen, Sangeeta Dhawan

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