Search for polymorphic variants of candidate genes contributing to individual radiosensitivity

Abstract

Background.Cytogenetic damage (СD) in lymphocytes induced by low doses (up to 0.1 Sv) of ionizing radiation (IR) is the main cytogenetic sign of individual radiosensitivity of the human body. In addition to DNA repair and cell death, which affect the formation of СD and its elimination, IR effects on the cell can be manifested through changes in proliferation of cells with unrepaired DNA damage. The system of cyclins and cyclin-dependent kinases (CDK), which provide coordination of mitotic events during passage of a cell through the cell cycle, plays a crucial role in regulation of cell proliferation.Aim.To evaluate the relationship of single-nucleotide polymorphisms (SNPs) of cell cycle genes with an increased frequency of СD in workers of a nuclear power plant affected by chronic occupational radiation exposure in the dose range of 100–500 mSv.Materials and methods.The object of the study was blood of 55 conditionally healthy workers of Siberian Chemical Plant (SCP) who were affected by chronic occupational radiation exposure (gamma radiation) in the dose range of 100–500 mSv. A standard cytogenetic analysis of blood lymphocytes was performed for all examined individuals. Genomic DNA was isolated from the blood of the workers using the QIAamp DNA Blood Mini Kit (QIAGEN, Germany). DNA was genotyped using 257 SNPs of cyclin genes and neighboring intergenic regions using DNA microarrays from the high-density CytoScan HD Array (Affymetrix, USA).Results.Taking into account the Bonferroni correction, only statistically significant associations of SNPs with the frequency of dicentric chromosomes were found; all other types of chromosomal aberrations did not show statistical significance. The rs803054CCNI2was associated with an increased frequency of dicentric chromosomes arising under the influence of chronic occupational radiation exposure.Conclusion.The discovered SNP (rs803054), whose recessive genotype is associated with an increased frequency of dicentric chromosomes in workers of SCP exposed to radiation at doses of 100–500 mSv over a long time, can be considered as a potential marker of individual radiosensitivity. To confirm the identified associations, further validation studies are needed on an expanded sample of people affected by chronic occupational radiation exposure.