MOLECULAR-GENETIC MECHANISMS IN DEVELOPMENT OF DEGREE OF FUNCTION AND HYPERPLASIA OF THYROID GLAND OF PATIENTS WITH NODULAR GOITER WITH AUTOIMMUNE THYROIDITIS AND THYROID ADENOMA

Abstract

Introduction. Autoimmune thyroiditis affects in average 2% to 5% of the general population, with young adult females and the elderly being the most vul-nerable patients. Hashimoto's thyroiditis causing hypothyroidism is the most prevalent etiology. Although genetics is well known to cause and influence the progression of autoimmune diseases in approximately 79%, other environmental factors are known to be involved in the development of autoimmune thyroid dis-eases: quantity of ingested iodine, stress, drugs, pregnancy, and changes in sexual hormones. Autoimmune thyroiditis, as a background disease of nodular goiter, in which hypothyroidism usually develops, has been insufficiently studied. Material and methods. The BCL-2 (rs17759659), CTLA-4 (rs231775), Fas (rs2234767) genes' polymorphism were studied by Real-Time Polymerase Chain Reaction in 95 patients with NGAIT, 30 patients with thyroid adenoma (TA) and 25 healthy individuals. The thyroid gland (TG) functional activity changes (nor-mal function, subclinical and clinical hypothyroidism) and TG hyperplasia degrees (IB, II and III) were analyzed. Results. TA and NGAIT are more common in the minor G-allele carriers (GА- and GG-genotypes) of the BCL-2 gene and in homozygous G allele patients (GG-genotype) of the Fas gene by 11.5 and 4.34 times (р<0.01), with no signifi-cant interdependence between the CTLA4 gene's genotypes. TG hyperplasia in patients' general cohort as well as in those with NGAIT is associated with the wild A alleles of the CTLA-4 gene (АА- and AG-genotypes): the І and ІІІ degree hy-perplasia occurred reliably more frequently in the AA genotype carriers, and ІІ degree of the TG enlargement in the AG genotype patients. Conclusions. Pathology of the thyroid gland has unreliable chances to be inherited depending on the polymorphism of BCL-2 (rs17759659), CTLA-4 (rs231775) and Fas (rs2234767) genes in Bukovina region (Western Ukraine). We did not find any difference between the relative incidences of the genotypes of the analyzed genes in the patients with NGAIT and those with TA or depending on the TG function (euthyroid goiter, subclinical and clinical hypothyroidism)..

Keywords

• nodular goiter with autoimmune thyroiditis
• thyroid adenoma
• functional state
• hyperplasia
• polymorphisms of apo-1 / fas
• ctla-4 and bcl-2 genes