ISSN ONLINE: 2558-815X
ISSN PRINT: 1584-9244
ISSN-L: 1584-9244

Effect of APO-1 / FAS, CTLA-4 and BCL-2 genes polymorphisms on the risk of goiter nodular forms with autoimmune thyroiditis occurrence among the Bukovinian population

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ABSTRACT
Introduction. Autoimmune thyroiditis (AIT) is one of the unsolved problems of modern endocrinology, as the issue of its insufficient etiology and pathogenesis comes now clear. Cytokines play an important role in the regulation of immune and inflammatory response, as the genes that encode them are seen as potential candidates for the risk of autoimmune thyroid pathology. However, a number of unsolved issues remains, in particular related to the role of genetic factors in the development of AIT.
Objectives. To analyze the frequency of polymorphic variants of genes BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1 / Fas (rs2234767) in patients with thyroid pathology regarding its forms: nodular goiter with autoimmune thyroiditis (NGAIT) and thyroid adenoma (TA).

Methods. The BCL-2 (rs17759659), CTLA-4 (rs231775), Fas (rs2234767) genes polymorphism was studied by Real-Time Polymerase Chain Reaction in 95 patients with NGAIT, 30 patients with TA and 25 healthy individuals. The thyroid gland (TG) functional activity changes (normal function, subclinical and clinical hypothyroidism) and TG hyperplasia degrees (IB, II and III) were analyzed.
Results. Mutation of BCL-2 (rs17759659) and CTLA-4 (rs231775) genes in the homozygous state among resident’s adult population of Northern Bukovina occurs with a frequency of 3.2-4.0%, no reliable difference between patients and healthy subjects. Mutations of the gene APO-1 / Fas (rs2234767) in the homozygous state are not observed. The nature of allelic distribution set: parity ratio between the main A and G minor alleles of the BCL-2 gene (52% versus 48% of patients; p> 0.05) and 54% against 46% – healthy subjects (p> 0.05)) A dominance of wild-allele mutation of the G-allele CTLA-4 gene 2.57 times among patients (2 = 96.8; p <0.001), and 3.54 times among healthy subjects (2 = 31.36; p <0.001); and the prevalence of G-allele mutation of the A-allele gene Fas – 9.87 times in patients (90.8% vs. 9.2%, p <0.001) and .7.33 times – in healthy subjects (88 % vs. 12%, (2 = 57.76; p <0.001).
Conclusions. Pathology of the thyroid gland in general 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).
Key words: nodular goiter, autoimmune thyroiditis, genes polymorphisms APO-1 / FAS, CTLA-4 and BCL-2.
Abbreviations: NGAIT – nodular goiter with autoimmune thyroiditis, AIT- autoimmune thyroiditis, TG – thyroid gland, TA – thyroid adenoma.

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Corresponding author:

M.I. Sheremet
Surgery Department No
1 of BSMU, 191 Golovna str, 58018 Chernovtsy, Ukraine
e-mail: mihayl71@gmail.com
phone – 0956064607

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