DNA methylation in monozygotic quadruplets affected by type 1 diabetes

Disanto, Giulio; Včeláková, Jana; Pakpoor, Julia; Elangovan, Ramyiadarsini; Šumnı́k, Zdenĕk; Ulmannová, Tereza; Ebers, George C.; Ramagopalan, Sreeram; Stechova, Katerina

doi:10.1007/s00125-013-2972-3

Cited by 17 publications

(23 citation statements)

References 11 publications

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“…Rakyan et al, showed that T1D-associated methylation variable positions (T1D-MVPs) are associated with the presence of islet autoantibodies and that these modifications are detectable before the diagnosis of disease [17]. A recent study on global DNA methylation in one set of MZ quadruplets discordant for T1D showed MVPs in diabetes-associated genes (INS-IGF2, SH2B3, MEG3 and ORMDL3) in the affected twins [18]. Genome-wide DNA methylation for T1D-associated nephropathy identified 19 potential CpG sites associated with risk for the disease [19].…”

Section: Discussionmentioning

confidence: 99%

DNA methylation profiles in type 1 diabetes twins point to strong epigenetic effects on etiology

Stefan

Zhang

Concepcion

et al. 2014

Journal of Autoimmunity

136

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Type 1 diabetes (T1D) shows ~ 40% concordance rate in monozygotic twins (MZ) suggesting a role for environmental factors and/or epigenetic modifications in the etiology of the disease. The aim of our study was to dissect the contribution of epigenetic factors, particularly, DNA methylation (DNAm), to the incomplete penetrance of T1D. We performed DNAm profiling in lymphocyte cell lines from 3 monozygotic (MZ) twin pairs discordant for T1D and 6 MZ twin pairs concordant for the disease using HumanMethylation27 BeadChip. This assay assesses the methylation state of 27,578 CpG sites, mostly located within proximal promoter regions. We identified 88 CpG sites displaying significant methylation changes in all T1D-discordant MZ twin pairs. Functional annotation of the genes with distinct CpG methylation profiles in T1D samples showed differential DNAm of immune response and defense response pathways between affected and unaffected twins. Integration of DNAm data with GWAS data mapped several known T1D associated genes, HLA, INS, IL-2RB, CD226, which showed significant differences in DNAm between affected and unaffected of twins. Our findings suggest that abnormalities of DNA methylation patterns, known to regulate gene transcription, may be involved in the pathogenesis of T1D.

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Section: Discussionmentioning

confidence: 99%

DNA methylation profiles in type 1 diabetes twins point to strong epigenetic effects on etiology

Stefan

Zhang

Concepcion

et al. 2014

Journal of Autoimmunity

136

View full text Add to dashboard Cite

show abstract

“…Similarly, it was reported that CD14+ and CD4+ cells of T1D quadruplets were hyper-and hypo-methylated [17]. In order to determine whether these methylation differences trigger the onset of T1D or are merely the results after the onset of diabetes [17], it is required to monitor the level of methylation periodically and to determine the discordant years in a long-term follow-up study.…”

Section: Epigenetic Mechanismmentioning

confidence: 98%

“…Although twin-studies on type 1 diabetes suggest that the abnormal DNA methylation might act as a pivotal part in the etiology of T1D, hypermethylation in CpG sites of some genes can be also observed in affected discordant twins [15]. Similarly, it was reported that CD14+ and CD4+ cells of T1D quadruplets were hyper-and hypo-methylated [17]. In order to determine whether these methylation differences trigger the onset of T1D or are merely the results after the onset of diabetes [17], it is required to monitor the level of methylation periodically and to determine the discordant years in a long-term follow-up study.…”

Section: Epigenetic Mechanismmentioning

confidence: 99%

Twin-Studies on the Role of Non-Genetic Factors in T1D Pathogenesis

Ma¹,

Wu²,

Dong³

et al. 2017

Proceedings of the 2nd International Conference on Biomedical and Biological Engineering 2017 (BBE 2017)

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Abstract. Type 1 diabetes (T1D) is a complex autoimmune disease characterized by T cell-mediated destruction of pancreatic β cells, which is resulted from the interaction of genetic and environmental factors. Twin-study is one of the most important methods to identify the genetic basis of complex diseases or traits as well as the influence of non-genetic factors in the pathogenesis of T1D. This article summarizes recent twin-studies about the role of non-genetic factors in T1D pathogenesis, including epigenetic mechanism, immunity, and complication factors. In addition, we discuss the potential necessity of the twin-study method in the research on the influence of the living environment on T1D.

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“…A pain sensitive meta-analysis (MA) highlighted Table 3 Epigenome-wide epigenetic studies in twins. The list is obtained from a Pubmed search with search terms 'Epigenetic,' 'twin,' 'DNA methylation,' 'histone, ' Baranzini et al, 2010;Baranzini, 2011;Bell et al, 2014;Bocklandt et al, 2011;Boks et al, 2009;Bonsch et al, 2012;Bonilla et al, 2013;Byrne et al, 2013;Davies et al, 2014;Dempster et al, 2011;Disanto et al, 2013;Fraga et al, 2005;Furukawa et al, 2013;Gervin et al, 2012;Gordon et al, 2012;Grundberg et al, 2013;Heyn et al, 2013;Javierre et al, 2010;Jin et al, 2014;Kaminsky et al, 2008;Kaminsky et al, 2009;Kinoshita et al, 2013;Letourneau et al, 2014;Martino et al, 2013;Marsit et al, 2013;Miyake et al, 2013;Nguyen et al, 2010;Nitert et al, 2012;Rakyan et al, 2010;Rakyan et al, 2011a;Ribel-Madsen et al, 2012;Sarachana et al, 2010;Selmi et al, 2012;Stefan et al, 2014;Te et al, 2010;Umeton et al, 2011;Wong et al, 2013;Yu et al, 2012. Twin Studies and Epigenetics nine MAP-DMRs of which one was in the promoter of TRPA1, an established pain-sensitivity gene. T...…”

Section: Epigenome-wide Association Scans For Complex Traits and Disementioning

confidence: 99%