The Role of Transforming Growth Factor-ß1 Gene Polymorphism and Its Serum Levels in Hashimoto's Thyroiditis.

BACKGROUND: TGF-ß1 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-ß1 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-ß1 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.

Clinical significance of autoantibodies to parietal cells in patients with autoimmune thyroid diseases.

UNLABELLED: Clinical significance of autoantibodies to parietal cells (PCA) in patients with autoimmune thyroid diseases (ATD) remains contradictory. AIM: To characterize the frequency of PCA in patients with ATD; to clarify the role of gender and age in PCA positivity; to analyze the association of PCA with gastric or haematologic symptoms and with the levothyroxine dose required to achieve a serum TSH level within the normal range in treated Hashimoto's thyroiditis (HT) patients. PATIENTS AND METHODS: PCA were measured using ELISA in 137 HT patients, divided into tree subgroups according to the thyroid function: group I included subjects with normal thyroid function; group II included patients with hypothyroidism, in group III were enrolled subjects treated with levothyroxine (LT4). We also studied the PCA positivity in 14 patients with active Graves' disease and in 23 healthy controls. RESULTS: PCA positivity was found in 51 patients with autoimmune thyroid diseases, with an overall prevalence of 33.8%. No significant differences in PCA were observed between the groups of HT patients. The frequency of PCA in both genders was similar and there were no difference depending on age. In 7.3% of HT patients in different stages of disease we found clinically relevant gastric and/or haematologic symptoms; in 70% of them PCA were positive (OR = 5.5; 95% CI: 1.2 - 28.4; p = 0.009). PCA positive hypothyroid HT patients required higher LT4 doses than PCA negative (1.46 microg/kg vs 1.24 microg/kg, p = 0.04). CONCLUSIONS: PCA may be present in different stages in HT patients; this does not depend on the severity of disease. PCA concentrations may predict symptoms of atrophic gastritis in patients with Hashimoto's thyroiditis. PCA positive HT patients require higher replacement doses of LT4. Presence of anemia, particularly microcytic anemia, was suggestive of undiagnosed atrophic gastritis.