Features of the polymorphism of the VEGFa G634C gene and the expression of the vasculodothelial growth receptor (CD304+) as risk factors for angiogenesis disorders in conditions of rare earth elements

Author:

Dolgikh Oleg V.1ORCID,Zaitseva Nina V.1ORCID,Letyushev Aleksandr N.2ORCID,Chelakova Yulia A.1ORCID

Affiliation:

1. Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

2. Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing; Russian Medical Academy of Continuous Professional Education

Abstract

Introduction. Preserving and strengthening the health of the working population of Russia is a priority task of occupational health. The study aims to research the features of polymorphism of the VEGFa G634C gene and expression of the vascular endothelial growth factor receptor (CD304+) as risk factors for angiogenesis disorders in workers exposed to rare earth elements. Materials and methods. The observation group included 46 people — employees of a non-ferrous metallurgy enterprise exposed to harmful chemical production factors — lanthanides (class of working conditions 3.1). The comparison group included 64 people who are not in contact with harmful production factors (administrative workers). The researchers have used immunological methods in the work: allergosorbent test with enzyme label, membrane immunofluorescence on a flow cytometer, IFA. For statistical processing of the study results, the authors have used the following criteria: Student's t-test, Mann–Whitney U-test, coefficient of determination (R2), relative risk index (RR), odds ratio (OR) and 95% confidence interval (CI). The authors considered the reliability of the differences to be significant at p<0.05 Results. In the observation group, the following were found: overexpression of lanthanide-specific IgG with an increase in the concentration of yttrium and cerium in the blood (R2=0.44 at p<0.05; OR=2.05; 95% CI=1.03–5.05) (RR=1.32; 95% CI=1.17–6.75); an increased expression level in relation to the comparison group of the neuropilin-1 CD304+ semaphorin receptor, which is also a receptor for vascular endothelial growth factor (VEGF), associated with an increase in the concentration of neodymium in the blood (R2=0.94 at p≤0.05; OR=1.27; 95% CI=1.06–3.84; RR=1.22; 95% CI=1.09–4.24). According to the results of the evaluation of the frequency of alleles and genotypes of the gene of the vascular endothelial growth factor VEGFa G634C (rs2010963), which controls the effects of the innate immune response (dendritic cells), the expression level of the G allele was significantly increased in relation to administrative workers (by 1.4 times), while the minor CC genotype was completely absent. Limitations. The limitations of this study were the limited sample size and the number of literary sources on the issue under study. Conclusion. In people working under the influence of harmful chemical factors — lanthanides (hazard class 3.1), experts have established the features of the expression of the VEGF gene and receptor: overexpression of the CD304+ lymphocyte cluster (HR=1.22; 95% CI=1.09–4.24), increased frequency of the G allele of the VEGFa gene (hazard class 3.1). The VEGFa G634C gene (OR=2.87; CI=1.16–7.07; OR=1.64(1.03–2.38); p<0.005), as well as an increase in the concentration of lanthanide-specific IgG (OR=2.05; 95% CI=1.03–5.05), which forms the risk of developing immunoassociated angiogenesis disorders associated with contamination of the biological environment with rare earth elements.

Publisher

FSBI Research Institute of Occupational Health RAMS

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