The autoimmune thyroid disease is a complex disorder caused by a combination of genetic susceptibility and environmental factors, which are believed to initiate the autoimmune response to thyroid antigens. Identification of the susceptibility genes has found that unique and diverse genetic factors are in association with Graves' disease and autoimmune thyroiditis. The thyroglobulin gene is an identified thyroid-specific gene associated to autoimmune thyroid disease and, principally, with autoimmune thyroiditis. The aim of this work was to test for evidence of allelic association between autoimmune thyroiditis and thyroglobulin polymorphism markers. We studied six polymorphisms distributed throughout all the thyroglobulin gene: four microsatellites (Tgms1, Tgms2, TGrI29 and TGrI30), one insertion/deletion (Indel) polymorphism (IndelTG-IVS18) and one exonic single nucleotide polymorphism (SNP) (c.7589G>A) in 122 patients with autoimmune thyroiditis compared with 100 non-related normal subjects. No differences in allele and genotype distribution were observed between autoimmune thyroiditis cases and controls for Tgms1, Tgms2, TGrI30, IndelTG-IVS18 and c.7589G>A. However, when we analyzed the patients with the TGrI29 microsatellite we found a significant association between the 199-bp allele and AT (33.7% vs. 24.5% in control group) (P = 0.0372). In addition, a higher prevalence of the 201-bp allele has been observed in control subjects (47.5% vs. 38.1% in patients group), although not statistically significant (P = 0.0536). Our work shows the association between the thyroglobulin gene and autoimmune thyroiditis and reinforce that thyroglobulin is a thyroid-specific susceptibility gene for this disease.

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1. A study was made of the activity of the enzyme thyroid peroxidase and of the concentration, carbohydrate composition and the degree of iodination of thyroglobulin in the thyroid glands of 60 patients with non-endemic non-toxic goitre in the nodular phase and in those of 25 control subjects. 2. Thyroid peroxidase activity was determined by the guaiacol assay and was significantly higher in patients with non-endemic non-toxic goitre than in control subjects (3.60 +/- 2.51 and 2.07 +/- 1.08 mumol of guaiacol oxidized min-1 g-1 of tissue, respectively; ranges 0.16-10.57 and 0.52-4.85 mumol of guaiacol oxidized min-1 g-1 of tissue, respectively; P less than 0.05). 3. Thyroglobulin was purified by precipitation with ammonium sulphate and Sephadex G-200 gel filtration. Two protein peaks were obtained which were identified as thyroglobulin and measured by radioimmunoassay. The concentration of thyroglobulin in the first peak was 98.94 (SD 84.87, range 0.60-455.54) mg/g of tissue for the patients with non-endemic, non-toxic goitre and 51.41 (SD 28.34, range 14.99-106.39) mg/g of tissue for the control subjects (P less than 0.01). The second peak showed 1.26 (SD 1.27, range 0.09-6.50) mg of thyroglobulin/mg of tissue for the group with non-endemic non-toxic goitre and 0.51 (SD 0.25, range 0.15-0.98 mg of thyroglobulin/mg of tissue) for the control subjects (P less than 0.01). 4. The carbohydrate composition of thyroglobulin was determined by acid hydrolysis and colorimetry, evaluating the levels of hexoses, hexosamines and sialic acid.(ABSTRACT TRUNCATED AT 250 WORDS)