DICER and DROSHA gene expression and polymorphisms in autoimmune thyroid diseases

Area of Science:

• Genetics
• Molecular Biology
• Immunology

Background:

• Dicer and Drosha are essential RNase III enzymes for microRNA biogenesis.
• Their association with autoimmune thyroid disease (AITD) pathogenesis has not been previously reported.
• Autoimmune thyroid diseases, including Hashimoto's disease (HD) and Graves' disease (GD), are common endocrine disorders.

Purpose of the Study:

• To investigate the potential association between Dicer and Drosha gene polymorphisms and AITD.
• To examine the expression levels of Dicer and Drosha genes in patients with AITD.
• To explore the correlation between gene expression and disease characteristics.

Main Methods:

• Genotyping of DICER (rs3742330, rs1057035) and DROSHA (rs644236, rs10719) polymorphisms using PCR-RFLP.
• Quantitative RT-PCR (qRT-PCR) to measure DICER and DROSHA gene expression in peripheral blood mononuclear cells (PBMCs).
• Study population included 255 HD patients, 255 GD patients, and 128 healthy controls.

Main Results:

• The TT genotype of DICER rs1057035 was less frequent in GD patients compared to controls (p=0.0098).
• The CC genotype of DROSHA rs644236 was more frequent in GD patients than in HD patients (p=0.0171).
• Lower gene expression of DICER and DROSHA was observed in AITD patients compared to controls (p=0.0064 and p<0.0001, respectively).
• DICER expression was lower in GD remission patients than in intractable GD patients (p=0.0213).
• DROSHA expression was lower in severe HD patients than in mild HD patients (p=0.0440).

Conclusions:

• DICER rs1057035 TT genotype is associated with the development of Graves' disease.
• DROSHA rs644236 CC genotype may help differentiate between Graves' disease and Hashimoto's disease.
• Reduced expression of DICER and DROSHA genes is characteristic of AITD and correlates with disease activity and severity.