FREQUENCY OF POLYMORPHIC GENE VARIANTS IN PATIENTS WITH AUTOIMMUNE THYROIDITIS AND THYROID ADENOMA
DOI:
https://doi.org/10.11603/2415-8798.2017.2.7849Keywords:
nodular colloidal goiter on the background of autoimmune thyroiditis, thyroid adenoma, functional state, hyperplasia, polymorphisms of APO-1 / FAS, CTLA-4 and BCL-2 genes.Abstract
Nowadays, the issues of etiology, pathogenesis, diagnosis and surgical treatment of such a combined pathology as nodular goiter and autoimmune thyroiditis (AIT) remain relevant. Autoimmune thyroiditis, as a background disease of nodular goiter, in which hypothyroidism almost always develops, has not yet been studied enough. Timely and accurate diagnosis of nodular forms of goiter against the background of autoimmune thyroiditis is important in the choice of the method of treatment of nodular thyroid pathology, indications, volume and nature of surgical treatment. All this causes the urgency of studies aimed at studying the features of pathogenesis and the course of nodular colloidal goiter against the background of autoimmune thyroiditis (NCGAIN). The presence of family forms of the disease and genealogical research data is evidence of the important role of the genetic factor in the pathogenesis of AIT [1011]. Confirming their opinion that as a result of a complete genetic scan, some loci associated with AIT were found, with the genes HLA (human leukocyte antigen) of the system and protein-4 associated with cytotoxic T-cells playing a key role in the predisposition, Lymphocytes (Cytotoxic T lymphocyte-associated-protein 4, CTLA4) [12-17]. But the influence of these genes on the overall genetic predisposition to AIT is only about 5 %.
The aim of the study – to conduct an analysis of the frequency of polymorphic variants of the genes BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1 / Fas (rs2234767) in patients with thyroid gland pathology, taking into account its type (BACK, ASHP-adenoma of the thyroid gland), changes in functional active thyroid gland (euthyroidism, subclinical and clinical hypothyroidism) and the degree of thyroid gland enlargement (IB, II and III items).
Materials and Methods. The frequency of polymorphic variants of the genes BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1 / Fas (rs2234767) in 125 patients operated on the thyroid nodular pathology with its species taken into account – changes in functional activity of the thyroid gland (euthyroidism, subclinical and clinical hypothyroidism) and the degree of thyroid gland enlargement (IB, II and III century). Also, 25 practically healthy donors were examined. Investigation of gene polymorphism was carried out by real-time polymerase chain reaction.
Results and Discussion. Hyperplasia of the thyroid gland in patients in general, as well as in such with NGAIT, is associated with the wild A gene of the CTLA-4 gene (AA and AG genotypes): IB and III degree of hyperplasia were significantly more frequent in carriers of the AA genotype by 30.13 % and 26–35 % (χ2= 9.26, p = 0.01), and the degree of thyroid gland enlargement in patients with AG genotype is 33.52 % and 34.04 % (χ2= 12.34; P = 0.002), respectively. The pathology of the thyroid gland as a whole has an unreliable chance of inheritance depending on the polymorphism of the genes BCL-2 (rs17759659), CTLA-4 (rs231775) and APO-1 / Fas (rs2234767).
Conclusions. The presence of a polymorphic variant of the CTLA-4 gene in the genome of a patient with an AG increases the risk of hyperplasia of the thyroid gland of the second degree twice (OR = 4.69, 95 % CI OR: 1.60–13.69, p = 0.004), whereas the carriage of the main allele in the homozygous state (AA-genotype), on the contrary, is effective preventive and makes the chances of hyperplasia of the thyroid gland of II-degree low in the surveyed population (OR = 0.46, 95 % CI OR: 0.09–0.73, p = 0.009). The remaining polymorphisms of the analyzed genes do not associate with risk neither NСGAIT, TA, nor thyroid function, or the degree of its increase.
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