The roles of genes of ksenobiotics biotransformation in the development of predisposition to the toxic heoatitis in workers workers exposed to hepthyle and ethylebenzene-styrene.



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Abstract

Introduction: The aim of this study was to estimate the predisposition of influencing possible factors causing chemical induced abnormal liver function on the basis of studying genes encoding xenobiotic metabolizing enzymes. Methods: Genotyping of CYP1A1, CYP2D6, CYP2E1, EPHX1, NAT2 was performed using polymerase chain reaction and restriction fragment length polymorphism on peripheral leucocyte DNA from 73 incident cases of toxic hepatitis, 163 «groups of risk» on development of a toxic hepatitis, 94 healthy workers and 335 controls.Results and conclusions: No significant association was found between a reference group and petrochemical workers when CYP1A1, CYP2D6, CYP2E1, EPHX1 genotypes were included in the analyses. Among workers was observed the increasing of frequency of a combination *4/*4 genes NAT2 compared with control group. Among the patients with a professional toxic hepatitis are established genetic markers of predisposition to development the disease: Ile/Val gene CYP1A1, Tyr/His gene EPHX1; combinations *4/*7 genes NAT2; and as slow phenotype microsomal epoxide hydrolase; combinations of genotypes IleVal/C1C1 of genes CYP1A1 and CYP2E1; combinations of slow phenotypes microsomal epoxide hydrolase and N-acetyltransferase-2. Our results suggest that genotype Ile/Ile of gene CYP1A1; genotype Tyr/Tyr of gene EPHX1; and as a normal phenotype microsomal epoxide hydrolase; a combination of genotypes IleIle/C1C1 of genes CYP1A1 and CYP2E1; a combination of genotypes IleIle/C1C1/CC/N of genes CYP1A1, CYP2E1, CYP2D6 and a normal phenotype microsomal epoxide hydrolase are protective variants. This study demonstrates a significant combined effect of phase I and phase II polymorphisms on the predisposition of professional pathology at workers exposed to hepthyle and ethylebenzene-styrene.

About the authors

Olga V Kochetova

Institute of Biochemistry and Genetics, Ufa Research Scientific Center RAS, Ufa, Republic of Bashkortostanб RF

Email: Olga_MK78@mail.ru

Tatyana V Victorova

Institute of Biochemistry and Genetics, Ufa Research Scientific Center RAS, Ufa, Republic of Bashkortostanб RF

Email: t_vict@mail.ru

Lilya K Karimova

Institute of Industrial Medicine and Human Ecology, Ufa, Republic of Bashkortostanб RF

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