DNA methylation analysis within the IL2RA gene promoter in youth with autoimmune thyroid disease

Abstract

Background Alpha‐subunit of the interleukin‐2 receptor (IL2RA) is involved in the regulation of T‐cell function and has been related to autoimmune thyroid disease (AITD). Although the exact mechanisms are not fully understood, promoter methylation might account for differences in gene expression. The aim of this study was to investigate whether there are differences in the percentage of DNA methylation within the IL2RA gene promoter in young patients with AITD. Materials and methods In a cross‐sectional design, the presence of DNA methylation in the IL2RA gene promoter was quantified, by real‐time PCR and melting curve analysis, in modified genomic DNA isolated from blood samples of a total of 149 children and adolescents with AITD, including patients with Hashimoto thyroiditis (ΗΤ) (n = 60), Graves' disease (GD) (n = 9), concurrent diagnosis of HT and type 1 diabetes (T1DM + HT) (n = 25), and healthy controls (n = 55). Results The percentage of DNA methylation in the IL2RA gene promoter was significantly decreased in patients with GD (26.0 ± 4.2%) but not in those with HT (36.3 ± 1.4%) in comparison with controls (41.3 ± 1.5%). Conclusions The observed DNA hypomethylation in the IL2RA gene promoter in patients with GD might be related to its increased expression, thus contributing to the etiopathogenesis of GD in childhood and adolescence.

Regulatory T Cells-Related Genes Are under DNA Methylation Influence

“…Moreover, the CpG methylation pattern did not differ between the T1D cells and control groups, and upon activation, the naïve T cells underwent demethylation in PRRVI and +3502 CpG [133]. Samples analysis of whole blood from patients with autoimmune thyroid diseases (AITDs), in this case Hashimoto thyroiditis or Graves' disease, have shown general hypomethylation in the promoter region in the latter [134]. Similar results from PBMC-derived samples have shown hypomethylation of the Il2ra promoter in children with obesity-associated asthma, which could be connected with inflammation in these patients [135].…”

Regulation of the cellular redox state and the expression of DNA methyltransferase-1 in peripheral blood mononuclear cells from patients with Graves’ disease

“…In agreement with our data, Limbach et al found, in CD4+ and CD8+ cells from patients with Graves' disease, hypermethylated CpG sites in genes involved in T cell signalling. 36 Other authors have found both hypermethylation 30,37 and hypomethylation 30,37,38 in genes involved in the immune and inflammatory response in peripheral blood leukocytes from patients with Graves' disease.…”

Molecular Mechanisms in Autoimmune Thyroid Disease

“…For instance, the hypomethylation within the IL-2Rα promoter could alter the IL-2Rα expression on Tregs, which competitively binds IL-2 and thereby plays a key role in the development and immunosuppressive function of Tregs. Thus, epigenetic alterations in the region of the IL-2Rα may explain its association with AITD; however, these alterations do not necessarily extrapolate to both extremes of AITD, as they appear to be more prevalent in individuals with GBD than in patients with HT, which is probably due to the underlying mechanisms in one disease or the other [ 152 , 153 ].…”