Polymorphism of the <i>VEGFA</i> (rs2010963) gene and low-dose exposure to airborne nickel as modification factors of programmed cell death in the Far North residents

Abstract

Introduction. Special relevance should be assigned to investigating a phenomenon of programmed cell death in working age population in the Far North exposed to airborne metals and sub-Arctic climate, with gene polymorphism taken into account.Materials and methods. We examined adult participants (aged 21–59 years) who lived on territories with subarctic and continental type of climate with different levels of exposure to airborne nickel (n=525). Nickel levels were identified in blood using inductively coupled plasma mass spectrometry; cell death indicators AnnexinV-FITC+7AAD– and AnnexinV-FITC+7AAD+ – were established with flow cytometry; vascular endothelial growth factor VEGF, immune enzyme assay; IgE to nickel, allergosorbent tests; VEGFA (rs2010963) gene polymorphism, real-time PCR.Results. The immune profile in adults living in the Far North under low-dose exposure to airborne nickel (1.36 ∙ 10-³ mg/(kg ∙ day); 0.12 average daily MPC) and with resulting nickel in blood (0.0123±0.0015 µg/cm³) was characterized with excess levels of AnnexinV-FITC+7AAD+ (R²=0.404–0.503; p=0.029–0.042) and IgE to nickel (R²=0.613; p=0.001). However, exposure to airborne nickel in sub-Arctic climate leads to relative risk RR=1.19 (1.03–1.36); p=0.005) for apoptosis inhibition per the level of AnnexinV-FITC+7AAD– (R²=0.723–0.786; p=0.001–0.016). This risk is associated with the minor C-allele and CC-genotype of the VEGFA (rs2010963) (OR=1.91 (1.03–3.55)–2.93 (1.31–6.57).Limitations. The reference group samples are limited; the results should be verified in future research Conclusion. Exposure to airborne nickel in the average daily dose of 1.36 ∙ 10–³ mg/(kg ∙ day), combined with the minor C-allele and CC-genotype of the VEGFA (rs2010963) induces changes in indices of cell death and the immune profile in adults in the Far North (declining AnnexinV-FITC+7AAD– levels, growing levels of VEGF and IgE to nickel). These genetic and immunological indices can be recommended as key ones in pre-nosologic diagnostics and disease prevention in the far North population. Compliance with ethical standards. The study was accomplished in conformity with ethical standards stipulated by the Declaration of Helsinki and approved by the local ethics committee of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies (Meeting Report No. 4 dated April 20, 2025). All participants gave informed voluntary written consent to participate in the study.Contributions: Zaitseva N.V. – study concept and design; Nikonoshina N.А. – data collection and analysis, writing the text; Dolgikh О.V. – study concept and design, editing the text; Alikina I.N., Kazakova О.А. – immunogenetic studies; Chigvintsev V.М. – mathematical modeling. All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.Conflict of interest. The authors declare no conflict of interest.Funding. The study had no sponsorship.Received: May 18, 2026 / Accepted: July 1, 2026 / Published: August 14, 2026