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, Clinic of Endocrinology, University Hospital, Stara Zagora, Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Stara Zagora, Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Stara Zagora
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.
