Polymorphism in ADD1 Gly460Trp rs4961 gene in workers exposed to occupational chemical factors (exemplified by saturated hydrocarbons)

Abstract

Introduction. Nowadays it has become especially vital to reveal basic regularities in workers’ health formation in order to provide early diagnostics and to reduce overall and occupational morbidity.
 The aim of the study was to examine polymorphism in ADD1 Gly460Trp rs4961 gene in workers exposed to chemical occupational factors at their workplaces (exemplified by saturated hydrocarbons).
 Materials and methods. We examined workplace air and biological media (urine and buccal epithelium) of exposed workers from the test group (n=162) and workers who didn’t deal with any technological processes at their workplaces (the reference group, n=83); both groups were employed at a potash flotation factory.
 To assess exposure to saturated hydrocarbons (hexane and heptane) in workplace air, we performed laboratory-instrumental tests of air inside workshops (11) and in administrative rooms with GANK-4 gas analyzer. Biological media (urine) were examined to determine contents of saturated hydrocarbons (hexane and heptane) in them by analyzing vapor phase in equilibrium on "Kristall-5000" gas chromatographer according to methodical Guidelines MUK 4.1.764-99.
 We analyzed polymorphism in ADD1 Gly460Trp rs4961 gene. Genetic typing was accomplished by polymerase chain reaction (PCR) in real time mode through allele discrimination with using TaqMan-probes on CFX96 (Bio-Rad) system as well as oligonucleotide primers and probes synthesized by "Sintol" company (Moscow).
 We applied Student’s t-test and Fischer’s Z-test to estimate authenticity of differences in obtained results. Pearson’s chi-square test (χ2) was used to check normalcy of quantitative data. We also assessed whether frequencies of candidate gene genotypes conformed to Hardy–Weinburg equilibrium.
 Results. Hexane was detected in workplace air in concentrations within 14–68 mg/m3 range (0.1MPCworkplace) during the observation period; heptane, 20–84 mg/m3 (0.1MPCworkplace). We assessed contamination of workers’ urine with hexane and heptane depending on their working experience that involved occupational contacts with saturated hydrocarbons, from 1 year and up to longer than 10 years. The assessment revealed that hexane contents were by 1.5 times higher and heptane contents by 1.22 times higher in workers with their working experience being longer than 10 years against workers with shorter working experience (less than 10 years).
 The results of a comparative analysis of the features of genetic polymorphism in the workers of the observation group in relation to the comparison group allowed us to establish significant differences between the frequencies of genotypes and alleles of the adducine gene ADD1 Gly460Trp rs4961, characterized by an increase in the frequency of the wild GG genotype of the gene. The assessment of the odds ratio (OR) of the presence in the observation group of the variation of the genotype GG of the gene ADD1 Gly460Trp rs4961 according to the multiplicative (for G allele inherited by dominant type OR=2.94; CI: 1.46–5.94; p<0.005) and general (for GG genotype, OR=3.14; CI: 1.44–6.86; p<0.005) inheritance models, as well as an assessment of the relative risk (for the G allele RR=1.38; CI: 1.23–1.53), allowed us to verify the reliable probability of the formation of genetically determined disorders associated with the development of arterial hypertension.
 Limitations. A limitation of the study is the study of the polymorphism of the ADD1 Gly460Trp rs4961 adducin gene only when exposed to two saturated hydrocarbons, hexane and heptane.
 Conclusion. Our research revealed that workers with basic production occupations and with working experience at the factory that was longer than 10 years had authentically higher hexane and heptane contents in their urine, by 1.5 (р<0.01) and 1.22 (р<0.048) times accordingly, than workers with their working experience at the factory being shorter than 10 years.
 We established that detection of hexane in concentrations equal to 0.006±0.002 mg/dm3 in urine of workers with basic production occupations who contacted saturated hydrocarbons vapors corresponded to 81% of the variation of the ADD1 Gly460Trp rs4961 gene in the form of a wild GG genotype (p<0.05) corresponded, which in conditions of contamination with marginal hydrocarbons can form the risk of cardiovascular pathology.
 Ethics. The research was performed in full conformity with ethical principles for medical research involving human subjects stipulated by the Declaration of Helsinki issued by the World Medical Association (the latest edition); all the participants gave their informed voluntary consent to take part in the research.