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