PP122. THE CYP1A2 AND NQO1 GENOTYPES ARE POSSIBLE FACTORS CAUSING CHEMICAL INDUCED ABNORMAL LIVER FUNCTION
O.V. KOCHETOVA Institute of Biochemistry and Genetics, Ufa, Russian Federation e-mail: Olga_makarova78@mail.ru
*Corresponding Author:
page: 103

Abstract

Hepthyle, ethylebenzene-styrene, benzene are hepatotoxic in humans. In vivo, these substances are metabolized by cytochromes P450 to form the electrophilic metabolites, which may either cause cell damage or be further metabolized and detoxified by glutathione S-transferases (GSTs) and NADPH: Quinone Oxidoreductase-1 (NQO1). This study investigated whether or not the genotypes CYP1A2 and NQO1 correlated with abnormal liver function found in petrochemical workers. For this study, 330 workers from the petrochemical plant were enrolled. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin was used as the parameter of liver function. The genotypes CYP1A2 (-164?→? and -2464?→delT) and NQO1 (C609T) were determined by polymerase chain reaction and restriction fragment length polymorphism on peripheral white blood cell DNA. We found that the CYP1A2*1D (T-2467delT) delT allele were associated with a 8,5-fold (95% CI: 1,1 - 75,0) risk increased AST and a 1,6-fold bilirubin (95% CI: 1,0 - 2,9). Combinations of genotypes CYP1A2 (-164?→? and -2464?→delT) AC/DD and CC/TD had an OR (95% CI) of 14,5 (1,8-31,0), 13,1 (1,6-28,7), 44,4 (5,5-97,1) on abnormal bilirubin, AST and ALT, respectively. TT NQO1 genotype was associated with decreased OR on abnormal bilirubin (OR 0,12; 95% CI: 0,01-0,9). These observations suggest that the two genotypes, CYP1A2 and NQO1, may play important roles in the biotransformation of hepatotoxic substances, the effect of which leads to liver damage.




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