Genetic Determinants of Radiosensitivity: Evidence of Radioresistance-Associated SNP Enrichment in Occupational Workers Chronically Exposed to Low-Dose Radiation

Botbayev, Dauren; Sharipov, Kamalidin; Belkozhayev, Ayaz; Alzhanuly, Bakhytzhan; Yerkinbek, Ulbossyn; Sharipov, Daulet; Gulyayev, Alexandr; Kairgeldina, Sayagul; Tekebayev, Kanat; Zhunussova, Gulnur; Baurzhan, Madina

doi:10.3390/genes17020191

Open AccessArticle

Genetic Determinants of Radiosensitivity: Evidence of Radioresistance-Associated SNP Enrichment in Occupational Workers Chronically Exposed to Low-Dose Radiation

by

Dauren Botbayev

^1,2,*

,

Kamalidin Sharipov

^2,3,

Ayaz Belkozhayev

^1,2

,

Bakhytzhan Alzhanuly

²,

Ulbossyn Yerkinbek

⁴,

Daulet Sharipov

⁵,

Alexandr Gulyayev

^6,7,

Sayagul Kairgeldina

⁶,

Kanat Tekebayev

⁶,

Gulnur Zhunussova

⁸

and

Madina Baurzhan

^6,*

¹

Department of Chemical and Biochemical Engineering, Geology and Oil-Gas Business Institute Named After K. Turyssov, Satbayev University, Almaty 050043, Kazakhstan

²

Structural and Functional Genomics Laboratory of M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, Almaty 050012, Kazakhstan

³

Department of Biochemistry, Asfendiyarov Kazakh National Medical University, Almaty 050000, Kazakhstan

⁴

Department of Biology, Faculty of Natural Sciences and Geography, Abai Kazakh National Pedagogical University, Almaty 050010, Kazakhstan

⁵

National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan

⁶

Ministry of Health of the Republic of Kazakhstan, Research Institute of Balneology and Medical Rehabilitation, Astana 010000, Kazakhstan

⁷

Laboratory of Drug Discovery and Development, Nazarbayev University, Astana 010000, Kazakhstan

⁸

Laboratory of Molecular Genetics, Institute of Genetics and Physiology, Almaty 050060, Kazakhstan

^*

Authors to whom correspondence should be addressed.

Genes 2026, 17(2), 191; https://doi.org/10.3390/genes17020191

Submission received: 10 January 2026 / Revised: 30 January 2026 / Accepted: 1 February 2026 / Published: 3 February 2026

(This article belongs to the Section Molecular Genetics and Genomics)

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Abstract

Background: Interindividual radiosensitivity is largely driven by genetic regulation of DNA damage recognition, repair, and cell-cycle control. TP53 and CDKN1A (p21) are key genomic markers associated with differential responses to ionizing radiation. Methods: This study investigated eight functional SNP markers across several key genes involved in DNA damage responses and cellular stress regulation, including TP53, CDKN1A/p21, APC, VEGF, XPD, and RAD51, in occupational groups exposed to chronic low-dose ionizing radiation at the Stepnogorsk Mining Chemical Combine and the Balkashinskoye uranium deposit. Genotyping was performed using PCR-based assays followed by restriction fragment length polymorphism (RFLP) analysis. Allele and genotype frequencies were compared between radiation-exposed workers and matched controls within Kazakh and Russian ethnic subgroups. Statistical differences were assessed using χ² tests, and associations with radioresistance were interpreted based on established functional characteristics of each polymorphism. Results: Four SNPs showed significant allele and genotype frequency shifts in radiation-exposed populations. The TP53 intron 3 insertion allele, TP53 intron 6 A allele, TP53 Pro72 (C) allele, and p21 codon 31 A allele were consistently enriched among exposed individuals. The strongest deviations were observed in Russian workers from Stepnogorsk (p < 0.01). These alleles are functionally associated with enhanced DNA repair efficiency, modified apoptotic responses, and strengthened cell-cycle checkpoint regulation. Conclusions: Significant enrichment of radioresistance-associated TP53 and CDKN1A (p21) variants was observed in uranium industry workers chronically exposed to low-to-moderate ionizing radiation. The observed patterns support a polygenic model of adaptive responses and emphasize the importance of genetic background in determining individual radiosensitivity under occupational exposure conditions.

Keywords: radioresistance; TP53; p21; chronic radiation exposure; radiogenomics; DNA damage response

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MDPI and ACS Style

Botbayev, D.; Sharipov, K.; Belkozhayev, A.; Alzhanuly, B.; Yerkinbek, U.; Sharipov, D.; Gulyayev, A.; Kairgeldina, S.; Tekebayev, K.; Zhunussova, G.; et al. Genetic Determinants of Radiosensitivity: Evidence of Radioresistance-Associated SNP Enrichment in Occupational Workers Chronically Exposed to Low-Dose Radiation. Genes 2026, 17, 191. https://doi.org/10.3390/genes17020191

AMA Style

Botbayev D, Sharipov K, Belkozhayev A, Alzhanuly B, Yerkinbek U, Sharipov D, Gulyayev A, Kairgeldina S, Tekebayev K, Zhunussova G, et al. Genetic Determinants of Radiosensitivity: Evidence of Radioresistance-Associated SNP Enrichment in Occupational Workers Chronically Exposed to Low-Dose Radiation. Genes. 2026; 17(2):191. https://doi.org/10.3390/genes17020191

Chicago/Turabian Style

Botbayev, Dauren, Kamalidin Sharipov, Ayaz Belkozhayev, Bakhytzhan Alzhanuly, Ulbossyn Yerkinbek, Daulet Sharipov, Alexandr Gulyayev, Sayagul Kairgeldina, Kanat Tekebayev, Gulnur Zhunussova, and et al. 2026. "Genetic Determinants of Radiosensitivity: Evidence of Radioresistance-Associated SNP Enrichment in Occupational Workers Chronically Exposed to Low-Dose Radiation" Genes 17, no. 2: 191. https://doi.org/10.3390/genes17020191

APA Style

Botbayev, D., Sharipov, K., Belkozhayev, A., Alzhanuly, B., Yerkinbek, U., Sharipov, D., Gulyayev, A., Kairgeldina, S., Tekebayev, K., Zhunussova, G., & Baurzhan, M. (2026). Genetic Determinants of Radiosensitivity: Evidence of Radioresistance-Associated SNP Enrichment in Occupational Workers Chronically Exposed to Low-Dose Radiation. Genes, 17(2), 191. https://doi.org/10.3390/genes17020191

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Genetic Determinants of Radiosensitivity: Evidence of Radioresistance-Associated SNP Enrichment in Occupational Workers Chronically Exposed to Low-Dose Radiation

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