The Role of Transforming Growth Factor-β1 Gene Polymorphism and Its Serum Levels in Hashimoto’s Thyroiditis

Title:The Role of Transforming Growth Factor-β1 Gene Polymorphism and Its Serum Levels in Hashimoto’s Thyroiditis

Volume: 19 Issue: 7

Author(s): Spaska A. Stanilova, Julieta B. Gerenova, Lyuba D. Miteva and Irena M. Manolova*

Affiliation:

• Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Stara Zagora,Bulgaria

Keywords: TGFB1, rs18000469, cytokine, Hashimoto’s thyroiditis severity, SNP, TGFB1 -509C/T Polymorphism.

Abstract: Background: TGF-β1 gene (TGFB1) is one of the target genes involved in genetic predisposition to autoimmune diseases, particularly Hashimoto’s thyroiditis (HT).

Objective: In the present study, we attempted to investigate whether -509C/T SNP (rs1800469) in the promoter of TGFB1 is associated with the genetic susceptibility and clinical characteristics of Bulgarian patients with HT. We also analyzed serum TGF-β1 levels in different stages of the disease and its association with the -509C/T polymorphism in the TGFB1 promoter.

Methods: The study recruited 121 female out-patients with autoimmune thyroiditis and 250 agematched healthy women (HC). Genotyping of the rs1800469 was performed by restriction fragment length polymorphism (RFLP)-PCR assay. The serum concentrations of latent acid-activated TGF-β1 protein were determined by the quantitative sandwich ELISA method.

Results: Upon testing different types of inheritance, a significant risk was found for heterozygotes (CT) with OR=1.640; p=0.05 under the codominant model. The significantly higher risk for developing Hypothyroidism was calculated again for CT-genotype patients with OR=1.789. According to the hormone reference values, a significant association of CT genotype with decreased TSH (75.4%) simultaneously with increased free T4 hormone (94%) levels was also calculated. When patients were stratified by genotype and compared to the same genotype in HC, we observed that the decreased levels in serum TGF-b1 were significant for patients who carried the C-allele in their genotype.

Conclusion: We suggest that heterozygous genotype CT is a genetic risk factor for developing more severe HT due to enhanced free T4 serum level at the onset of the disease, before developing the hypothyroid stage.

Cite this article as:

Stanilova A. Spaska , Gerenova B. Julieta , Miteva D. Lyuba and Manolova M. Irena *, The Role of Transforming Growth Factor-β1 Gene Polymorphism and Its Serum Levels in Hashimoto’s Thyroiditis, Current Pharmaceutical Biotechnology 2018; 19 (7) . https://dx.doi.org/10.2174/1389201019666180802142803