title: Genetic polymorphisms in metabolic enzymes and susceptibility to anti-tuberculosis drug-induced hepatic injury.
abstract: We examined the relationships between N-transacetylase 2 (NAT2), cytochrome P450 (CYP) 2E1 enzyme, glutathione S-transferase M1, T1 (GSTM1/GSTT1) gene polymorphisms, and anti-tuberculosis drug-induced hepatic injury (ADIH). A one-to-one matched case-control study was carried out using clinical data. NAT2, CYP2E1, GSTM1, and GSTT1 polymorphisms were identified in 173 pairs of research subjects. Statistical analysis was performed to determine risk factors of ADIH. The results showed that low body mass index and alcohol consumption were risk factors of ADIH, with odds ratios of 6.852 and 3.203, respectively. The frequencies of NAT2 slow acetylator, CYP2E1 -1259G>C, -1019C>T wild-type, and the GSTM1 null genotype were higher in the case group than in the control group, with odds ratios of 2.260, 2.696, 4.714, and 2.440, respectively. GSTT1 was not found to be related to ADIH. Interactive analysis showed that NAT2 slow acetylator and the GSTM1 null genotype were mutually synergistic, while an antagonistic relationship was observed between the CYP2E1 wild-type genotype and the other 3 genetic types. The risks of hepatic injury were higher after anti-tuberculosis therapy in patients carrying the NAT2 slow acetylator, CYP2E1 -1259G>C, -1019C>T wild-type, and GSTM1 null genotype.
authors.affiliation: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan, China fm_feng@sina.com.
authors.forename: F M
authors.initials: FM
authors.lastname: Feng
authors.affiliation: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan, China.
authors.forename: M
authors.initials: M
authors.lastname: Guo
authors.affiliation: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Tanshan Tuberculosis Hospital, Tangshan, China.
authors.forename: S M
authors.initials: SM
authors.lastname: Li
authors.affiliation: Tanshan Tuberculosis Hospital, Tangshan, China.
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.affiliation: College of Nursing and Rehabilitation, Hebei United University, Tangshan, China.
authors.forename: S F
authors.initials: SF
authors.lastname: Sun
authors.affiliation: Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan, China.
authors.forename: G S
authors.initials: GS
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology* / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1