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Genetic polymorphisms in metabolic enzymes and susceptibility to anti-tuberculosis drug-induced hepatic injury.
Genet Mol Res. 2014 Nov 11; 13(4):9463-71.GM

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+Show Affiliations

Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan, China fm_feng@sina.com.Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan, China.Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan, China.Tanshan Tuberculosis Hospital, Tangshan, China.Tanshan Tuberculosis Hospital, Tangshan, China.College of Nursing and Rehabilitation, Hebei United University, Tangshan, China.Key Laboratory of Occupational Health and Safety, School of Public Health, Hebei United University, Tangshan, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25501156

Citation

Feng, F M., et al. "Genetic Polymorphisms in Metabolic Enzymes and Susceptibility to Anti-tuberculosis Drug-induced Hepatic Injury." Genetics and Molecular Research : GMR, vol. 13, no. 4, 2014, pp. 9463-71.
Feng FM, Guo M, Chen Y, et al. Genetic polymorphisms in metabolic enzymes and susceptibility to anti-tuberculosis drug-induced hepatic injury. Genet Mol Res. 2014;13(4):9463-71.
Feng, F. M., Guo, M., Chen, Y., Li, S. M., Zhang, P., Sun, S. F., & Zhang, G. S. (2014). Genetic polymorphisms in metabolic enzymes and susceptibility to anti-tuberculosis drug-induced hepatic injury. Genetics and Molecular Research : GMR, 13(4), 9463-71. https://doi.org/10.4238/2014.November.11.11
Feng FM, et al. Genetic Polymorphisms in Metabolic Enzymes and Susceptibility to Anti-tuberculosis Drug-induced Hepatic Injury. Genet Mol Res. 2014 Nov 11;13(4):9463-71. PubMed PMID: 25501156.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic polymorphisms in metabolic enzymes and susceptibility to anti-tuberculosis drug-induced hepatic injury. AU - Feng,F M, AU - Guo,M, AU - Chen,Y, AU - Li,S M, AU - Zhang,P, AU - Sun,S F, AU - Zhang,G S, Y1 - 2014/11/11/ PY - 2014/12/16/entrez PY - 2014/12/17/pubmed PY - 2015/8/11/medline SP - 9463 EP - 71 JF - Genetics and molecular research : GMR JO - Genet Mol Res VL - 13 IS - 4 N2 - 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. SN - 1676-5680 UR - https://www.unboundmedicine.com/medline/citation/25501156/Genetic_polymorphisms_in_metabolic_enzymes_and_susceptibility_to_anti_tuberculosis_drug_induced_hepatic_injury_ L2 - http://www.geneticsmr.com/articles/3713 DB - PRIME DP - Unbound Medicine ER -