Exploring DNMT1 Polymorphism and Expression in the Hashimoto Thyroiditis Pathogenesis

Area of Science:

• Endocrinology and Immunology
• Molecular Biology and Genetics

Background:

• Hashimoto thyroiditis is an autoimmune disorder with genetic and environmental influences.
• DNA methylation, mediated by DNA methyltransferase 1 (DNMT1), is implicated in its pathogenesis.
• Investigating DNMT1's role in Hashimoto thyroiditis is crucial for understanding disease mechanisms.

Purpose of the Study:

• To examine the association between DNMT1 gene polymorphism (rs2228611) and gene expression in Hashimoto thyroiditis patients.
• To compare serum levels of thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase (anti-TPO) antibodies between patients and controls.
• To elucidate the molecular underpinnings of Hashimoto thyroiditis involving DNMT1.

Main Methods:

• A case-control study involving 50 Hashimoto thyroiditis patients and 50 healthy controls.
• Measurement of serum TSH and anti-TPO antibodies via ELISA.
• Analysis of DNMT1 gene expression using quantitative real-time PCR (qRT-PCR) and assessment of DNMT1 rs2228611 polymorphism via HRM-PCR.

Main Results:

• Hashimoto thyroiditis patients showed significantly higher TSH and anti-TPO levels (p < 0.0001).
• DNMT1 gene expression was upregulated by 1.7-fold in patients (p = 0.04).
• No significant differences in DNMT1 rs2228611 allelic or genotypic frequencies were observed, though the TT genotype trended towards increased risk (p = 0.07) and CT genotype suggested protection.

Conclusions:

• Elevated DNMT1 expression and thyroid dysfunction are characteristic of Hashimoto thyroiditis.
• The DNMT1 rs2228611 polymorphism may have a limited role in Hashimoto thyroiditis.
• Further research with larger cohorts is needed to confirm the influence of DNMT1 polymorphism.