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The pathogenesis and manifestation of autoimmune thyroid diseases (AITDs), Graves' disease (GD), and Hashimoto's disease (HD) are associated with T cell activation. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a crucial role in the regulation of T cell activation. DNA methylation levels of eight CpG sites in the CTLA4 gene and expression levels of soluble CTLA-4 were examined. Methylation levels of +22 CpG and CT60 CpG-SNPs in patients with GD and HD with the CT60 GG genotype were lower than those in control subjects. Methylation levels of the-15 CpG sites were lower in patients with intractable GD than those in GD patients in remission. These results suggest that demethylation of +22 CpG and CT60 CpG-SNPs may be associated with susceptibility to GD and HD in subjects with the CTLA4 CT60 GG genotype, and that demethylation of -15 CpG may be associated with the intractability of GD.
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Ohtani et al. (2024) studied this question.
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