The following is a summary of “DNA Methylation in Autoimmune Thyroid Disease,” published in the March 2023 issue of Endocrinology & Metabolism by Lafontaine, et al.
Graves disease and Hashimoto disease are types of autoimmune thyroid disease (AITD) influenced by genetic and environmental factors. Epigenetics is a potential mechanism linking environmental factors, gene expression, and the development of thyroid autoimmunity. Among epigenetic mechanisms, DNA methylation (DNAm) is the most studied, and global hypomethylation of leukocyte DNA has been observed in several autoimmune disorders.
The study provided an overview of the current knowledge of DNAm in AITD. Targeted studies of DNAm in blood samples from AITD patients have identified differential methylation in the promoter regions of various genes implicated in AITD, including TNF, IFNG, IL2RA, IL6, ICAM1, and PTPN22. However, many of these findings required replication and lacked supporting functional studies confirming their causal roles in AITD pathogenesis. In addition, thyroid hormones can influence DNAm, and reverse causation bias has yet to be adequately addressed in many studies.
Recent studies revealed that DNAm patterns in specific candidate genes, such as ITGA6, PRKAA2, and DAPK1, differed between AITD patients from regions with different iodine statuses, which suggested a potential mechanism for the association between iodine and AITD. Current research in the field was shifting towards a genome-wide approach to DNAm analysis. Genome-wide methylation studies of AITD patients have shown multiple differentially methylated positions, including some in immunoregulatory genes like NOTCH1, HLA-DRB1, TNF, and ICAM1.
Large-scale epigenome-wide studies were required to understand the pathophysiological role of DNAm in AITD fully and to provide novel diagnostic and prognostic biomarkers and therapeutic targets.
Source: academic.oup.com/jcem/article-abstract/108/3/604/6844010?redirectedFrom=fulltext
