Epigenome-wide Association Study Shows Differential DNA Methylation of MDC1, KLF9, and CUTA in Autoimmune Thyroid Disease.

Autor:	Lafontaine N; Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.; Medical School, University of Western Australia, Crawley, WA, 6009, Australia., Shore CJ; Department of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH, UK., Campbell PJ; Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia., Mullin BH; Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.; School of Biomedical Sciences, University of Western Australia, Perth, 6009, Australia., Brown SJ; Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia., Panicker V; Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.; Medical School, University of Western Australia, Crawley, WA, 6009, Australia., Dudbridge F; Population Health Sciences, University of Leicester, Leicester, LE1 7RH, UK., Brix TH; Department of Endocrinology and Metabolism, Odense University Hospital, Odense, 5000, Denmark., Hegedüs L; Department of Endocrinology and Metabolism, Odense University Hospital, Odense, 5000, Denmark., Wilson SG; Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.; Department of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH, UK.; School of Biomedical Sciences, University of Western Australia, Perth, 6009, Australia., Bell JT; Department of Twin Research & Genetic Epidemiology, King's College London, London, SE1 7EH, UK., Walsh JP; Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, 6009, Australia.; Medical School, University of Western Australia, Crawley, WA, 6009, Australia.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Mar 15; Vol. 109 (4), pp. 992-999.
DOI:	10.1210/clinem/dgad659
Abstrakt:	Context: Autoimmune thyroid disease (AITD) includes Graves disease (GD) and Hashimoto disease (HD), which often run in the same family. AITD etiology is incompletely understood: Genetic factors may account for up to 75% of phenotypic variance, whereas epigenetic effects (including DNA methylation [DNAm]) may contribute to the remaining variance (eg, why some individuals develop GD and others HD). Objective: This work aimed to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) comparing GD to HD. Methods: Whole-blood DNAm was measured across the genome using the Infinium MethylationEPIC array in 32 Australian patients with GD and 30 with HD (discovery cohort) and 32 Danish patients with GD and 32 with HD (replication cohort). Linear mixed models were used to test for differences in quantile-normalized β values of DNAm between GD and HD and data were later meta-analyzed. Comb-p software was used to identify DMRs. Results: We identified epigenome-wide significant differences (P < 9E-8) and replicated (P < .05) 2 DMPs between GD and HD (cg06315208 within MDC1 and cg00049440 within KLF9). We identified and replicated a DMR within CUTA (5 CpGs at 6p21.32). We also identified 64 DMPs and 137 DMRs in the meta-analysis. Conclusion: Our study reveals differences in DNAm between GD and HD, which may help explain why some people develop GD and others HD and provide a link to environmental risk factors. Additional research is needed to advance understanding of the role of DNAm in AITD and investigate its prognostic and therapeutic potential. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)
Databáze:	MEDLINE
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