COMPLEX ANALYSIS OF THE ROLE OF CYTOKINE GENE POLYMORPHISMS AS PROGNOSTIC FACTOR OF THE RISK OF PLASMA CELL MYELOMA IN PERSONS SUFFERED AFTER THE CHORNOBYL NPP ACCIDENT.

Abstract

Objective: to provide a comparative characterization of the prevalence of polymorphic variants of cytokine genes in plasma cell myeloma (PCM) patients suffered after the Chornobyl disaster and patients who were in contact with ionizing radiation within the natural radiation background, based on comparison with population controls to determine their contribution as genetic markers of disease risk.

Materials and methods: Molecular genetic studies of polymorphism of cytokine genes (TNF-α, TGF-β1, IL-6, IL-10, IFN-γ) and complex frequency analysis of occurrence in three-, four-, and five-locus combinations of their allelic variants as prognostic markers of the risks of plasma cell myeloma was carried out in 102 patients - 56 victims of the Chornobyl nuclear power plant accident and 46 patients irradiated within the limits of the natural radiation background, in comparison with the control group (364 practically healthy people, residents of the Central geno-geographical region of Ukraine).

Results: The same probable increase in the prevalence of the TGF-β genotype codon10 T/T of the TGF-β1 gene was established in the groups of patients irradiated after the Chornobyl NPP accident and non-irradiated patients. In patients with plasma cell myeloma a protective effect for IL-10 -1082 A/G and an association with the risk of disease occurrence for IL-10 -1082 G/G were determined.

Conclusion: Probable difference in the frequency of the TGF-β1 genotype codon10 T/T of the TGF-β1 gene in the observed groups relative to the control group provides grounds for considering this single-nucleotide polymorphism of the TGF-β1 gene as an immunogenetic factor of predisposition to the development of PCM independent of exogenous factors. The study of the contribution of multigene combinations of «gene-gene» interaction indicates their role in the mechanisms of plasma cell myeloma occurrence and confirms the presence of an additive interaction.