ESPE Abstracts

Background: Hashimoto Thyroiditis (HT) and Graves Disease (GD) are conditions known to be caused by abnormal immune response against self-tissues. The biological processes at molecular lever are still poorly understood. A few epigenetic studies have been published so far.

Objective: To investigate whether there are differences in DNA methylation within the HLADRB1, CD40L, FOXP3, CTLA4, FCRL3, IL2RA and PTPN22 promoters between young patients with autoimmune thyroid disease and healthy controls.

Material and Methods: Fifty-nine patients with HT (11.7±0.3 years), 9 with GD (12.0±0.4 years), 25 with concurrent type 1 diabetes (T1DM) and HT (13.8±0.5 years), and 54 healthy controls (11.1±0.3 years) without a personal or family history of autoimmune disease, at least at first-grade relatives, were recruited. DNA was extracted from whole blood and then modified with sodium bisulfite. The percentage of methylation in the above mentioned gene promoters was later quantified, using specific primers for modified DNA, by analyzing the melting curves obtained during real-time PCRs. Results are presented as 95% trimmed means±standard errors. Comparisons were performed using one-way ANOVA tests and Tukey’s post-hoc analyses. Level of statistical significance was set at P<0.05.

Results: Increased methylation percentage in PTPN22 promoter was associated with HT, decreased methylation percentage in IL2RA promoter with GD, while increased methylation percentage in CTLA4 promoter was associated with concurrent T1DM and HT. Percentages (%) of methylation in CpGs sites within different gene promoters between groups are shown below:

Conclusion: This study suggests that altered methylation percentages in different gene promoters do exist in patients with autoimmune thyroid disease. These differences remain to be shown whether they are related with variability in the expression of the corresponding genes, thus shedding light in the aetiopathogenesis of autoimmune thyroid disease in childhood and adolescence.