Exploring DNMT1 Polymorphism and Expression in the Hashimoto Thyroiditis Pathogenesis

Hashimoto thyroiditis is a chronic autoimmune disorder influenced by genetic and environmental factors. DNA methylation, regulated by DNA methyltransferase 1 (DNMT1), may play a critical role in its pathogenesis. This study investigated the association between DNMT1 polymorphism, particularly rs2228611, and gene expression in Hashimoto thyroiditis patients and also compared serum levels of thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase (anti-TPO) antibodies in both affected individuals and controls.

A case-control study of 100 participants (50 Hashimoto's thyroiditis patients and 50 controls) was conducted. TSH and anti-TPO levels were measured using the enzyme-linked immunosorbent assay (ELISA). DNMT1 expression was analyzed via quantitative real time-polymerase chain reaction (qRT-PCR), while DNMT1 (rs2228611 C/T) polymorphism was assessed by high-resolution melting-polymerase chain reaction (HRM-PCR).

The results revealed that Hashimoto thyroiditis patients exhibited significantly elevated serum TSH and anti-TPO levels compared to healthy controls (p < 0.0001). DNMT1 gene expression was upregulated by 1.7-fold in patients relative to controls (p = 0.04), suggesting a potential role in disease pathogenesis. Genotyping of DNMT1 rs2228611 polymorphism revealed no significant differences in allelic or genotypic frequencies between groups. However, the TT genotype showed a non-significant trend toward increased disease risk (p = 0.07). The CT genotype appeared to confer a protective effect.

The study's findings suggest that elevated DNMT1 expression and thyroid dysfunction are characteristic of Hashimoto thyroiditis, while the DNMT1 rs2228611 polymorphism may have a limited but possible influence, warranting further study with larger cohorts.