Однонуклеотидные полиморфизмы как биомаркеры отдалённых радиационно-индуцированных изменений системного иммунитета

A. A. Akleyev; E. A. Blinova; A. V. Akleyev

doi:10.25557/2310-0435.2021.03.38-49

A. A. Akleyev South Ural State Medical University, Chelyabinsk, Russia; Urals Research Center for Radiation Medicine of the Federal Biomedical Agency of Russia, Chelyabinsk, Russia http://orcid.org/0000-0001-9781-071X
E. A. Blinova Urals Research Center for Radiation Medicine of the Federal Biomedical Agency of Russia, Chelyabinsk, Russia; Chelyabinsk State University, Chelyabinsk, Russia http://orcid.org/0000-0002-2567-7945
A. V. Akleyev Urals Research Center for Radiation Medicine of the Federal Biomedical Agency of Russia, Chelyabinsk, Russia; Chelyabinsk State University, Chelyabinsk, Russia http://orcid.org/0000-0003-2583-5808

DOI: https://doi.org/10.25557/2310-0435.2021.03.38-49

Keywords: biomarkers, single-nucleotide polymorphisms, immune system, radiation, long-term effects

Abstract

Background. The search for molecular genetic predictors for malignant neoplasms is important for both understanding of pathogenetic mechanisms for long-term consequences of low dose and low dose rate exposure of people, and for personification of their radiation risk.

The aim was to study the connection of single-nucleotide polymorphisms (SNP) of genes regulating immune responses with systemic immune parameters in exposed persons in the long-term.
Methods. 384 residents of the Techa riverside settlements were examined 60 and more years after the onset of chronic exposure to a wide range of doses (range of individual values: 0.08-4.46 Gy). Effects of carrying SNP genes (PAD4 rs874881, MPO rs2333227, NOX2 rs4673, as well as IL1b rs1143634, IL2 rs2069762, IL4 rs2070874, IL6 rs1800795, IL8 rs4073, IL10 rs1800871, IL10 rs1800872, TNFα rs361525, MAPK8 rs2239815, STAT3 rs1053023, GATA3 rs4143094 and NF-κB1 rs28362491) on systemic immune parameters were studied.
Results. MAPK8 rs2239815, NF-κB1 rs28362491, STAT3 rs1053023 and GATA3 rs4143094 gene polymorphisms exerted a modifying effect on the number of main subpopulations of peripheral blood lymphocytes; IL10 rs1800872 and PAD4 rs874881, respectively, modified serum concentrations of IL-10 and TNFα. Polymorphisms IL2 rs2069762, IL6 rs1800795, IL12 rs3212227 and MPО rs2333227 modified the functional status of immunocompetent cells in exposed persons in the long-term.
Conclusion. Single-nucleotide polymorphisms of the genes involved in immune regulation can be considered as potential biomarkers associated with radiation-induced changes in the systemic immunity and as predictors for long-term consequences in exposed persons, primarily for malignant neoplasms.

Single-nucleotide polymorphisms as biomarkers of long-term radiation-induced changes in systemic immunity

Abstract