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Caspase-dependent mechanisms and antioxidant defense in the thyroid tissue of patients with nodular goiter with autoimmune thyroiditis and thyroid adenoma according to allelic status of BCL-2 (RS17759659), CTLA-4 (RS231775), APO-1 / FAS (RS2234767) genes

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ABSTRACT
Introduction. In the process of their vital activity, the cells are exposed to many damaging factors of endogenous and exogenous nature. It is undoubtedly that various toxic influences or metabolic disorders lead to the development of oxidative stress, and in this case the future of the cell is determined by a balance of various adaptive metabolic processes induced by a pathological factor, as well as by genetic and constitutional features of its biochemical systems.

Objectives. To analyze the mechanisms of caspase-dependent apoptosis and pro- and antioxidant activity in the thyroid tissue homogenate in patients with NGAIT and TA considering the polymorphic variants of BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1 / Fas (rs2234767) genes.
Methods. We investigated pro- and antioxidant activity and the activity of caspases 3 and 8 in 5% of thyroid tissue homogenates. 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.
Results. In homozygous carriers of A-allele of the BCL-2 (rs17759659) gene, the activity of effector caspase- 3 is higher than in the control group.
Conclusions. The imbalance between the activity of peroxidation and antioxidant defense in patients with
NGAIT and TA is associated with the promoter of the CTLA-4 (rs231775) and APO-1 / Fas (rs2234767) genes and is characterized by an increasing degree of OMP in the altered thyroid tissue and also with a lower capacity of the AOP system enzymes.
Key words: goiter, thyroiditis, caspases, oxidant status, genetic association.
Abbreviations: NGAIT – nodular goiter on the background of autoimmune thyroiditis; TG – thyroid gland, TA – thyroid adenoma, OMP – oxidative modification of proteins, AOP – antioxidant protection.

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Michael Ivanovich Sheremet, Larysa Petrivna Sydorchuk, Viktor Oleksandrovich Shidlovskyi, Anatoly Dmitrovich Bedenyuk, Olexander Viktorovich Shidlovsky, Vitaliy Vasilyovich Maksymyuk, Volodymyr Volodymyrovich Bezruk, Yan Viktorovich Gyrla, Tetyana Oleksandrivna Bezruk, Volodymyr Volodymyrovich Tarabanchuk, Viktor Markiyanovich Batig, Oleksandr Viktorovych Mytchenok, Kristina Andreyvna Chympoi and Marina Dmitryvna Gresko

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