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Genetic polymorphisms of manganese superoxide dismutase, NAD(P)H:quinone oxidoreductase, glutathione S-transferase M1 and T1, and the susceptibility to drug-induced liver injury.
J Hepatol. 2007 Jul; 47(1):128-34.JH

Abstract

BACKGROUND/AIMS

Drug metabolizing enzymes may be related to drug-induced liver injury (DILI). Manganese superoxide dismutase (MnSOD), NAD(P)H:quinone oxidoreductase (NQO1), and glutathione S-transferase (GST) are important drug metabolizing enzymes. We aimed to elucidate the relationship between genetic polymorphisms of these enzymes and the susceptibility to DILI.

METHODS

A total of 115 patients with DILI and 115 drug-, sex-, and age-matched controls were enrolled. Their genetic polymorphisms of MnSOD, NQO1, GSTM1, and GSTT1 were assayed.

RESULTS

Sixty-three (54.8%) of DILI patients were incriminated to anti-tuberculosis drugs. Subjects with a mutant C allele (T/C or C/C genotype) of MnSOD had a higher risk of DILI than those with MnSOD T/T genotype, both in overall drugs studied (adjusted OR: 2.44, 95% C.I.: 1.38-4.30, P=0.002), and in sub-category of anti-tuberculosis drugs (adjusted OR: 2.47, 95% C.I.: 1.13-5.39, P=0.02). In addition, subjects carrying GSTM1 null genotype had increased risk of anti-tuberculosis DILI (adjusted OR: 2.23, 95% C.I.: 1.07-4.67, P=0.03).

CONCLUSIONS

The MnSOD mutant C allele may increase the susceptibility to DILI, and GSTM1 null genotype may be related to anti-tuberculosis drug-induced hepatotoxicity. Determination of the MnSOD and GSTM1 genotypes may help identify patients at high risk for DILI.

Authors+Show Affiliations

Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan. yshuang@vghtpe.gov.twNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17400324

Citation

Huang, Yi-Shin, et al. "Genetic Polymorphisms of Manganese Superoxide Dismutase, NAD(P)H:quinone Oxidoreductase, Glutathione S-transferase M1 and T1, and the Susceptibility to Drug-induced Liver Injury." Journal of Hepatology, vol. 47, no. 1, 2007, pp. 128-34.
Huang YS, Su WJ, Huang YH, et al. Genetic polymorphisms of manganese superoxide dismutase, NAD(P)H:quinone oxidoreductase, glutathione S-transferase M1 and T1, and the susceptibility to drug-induced liver injury. J Hepatol. 2007;47(1):128-34.
Huang, Y. S., Su, W. J., Huang, Y. H., Chen, C. Y., Chang, F. Y., Lin, H. C., & Lee, S. D. (2007). Genetic polymorphisms of manganese superoxide dismutase, NAD(P)H:quinone oxidoreductase, glutathione S-transferase M1 and T1, and the susceptibility to drug-induced liver injury. Journal of Hepatology, 47(1), 128-34.
Huang YS, et al. Genetic Polymorphisms of Manganese Superoxide Dismutase, NAD(P)H:quinone Oxidoreductase, Glutathione S-transferase M1 and T1, and the Susceptibility to Drug-induced Liver Injury. J Hepatol. 2007;47(1):128-34. PubMed PMID: 17400324.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic polymorphisms of manganese superoxide dismutase, NAD(P)H:quinone oxidoreductase, glutathione S-transferase M1 and T1, and the susceptibility to drug-induced liver injury. AU - Huang,Yi-Shin, AU - Su,Wei-Juin, AU - Huang,Yi-Hsiang, AU - Chen,Chih-Yen, AU - Chang,Full-Young, AU - Lin,Han-Chieh, AU - Lee,Shou-Dong, Y1 - 2007/03/06/ PY - 2006/11/12/received PY - 2007/01/25/revised PY - 2007/02/08/accepted PY - 2007/4/3/pubmed PY - 2007/9/14/medline PY - 2007/4/3/entrez SP - 128 EP - 34 JF - Journal of hepatology JO - J Hepatol VL - 47 IS - 1 N2 - BACKGROUND/AIMS: Drug metabolizing enzymes may be related to drug-induced liver injury (DILI). Manganese superoxide dismutase (MnSOD), NAD(P)H:quinone oxidoreductase (NQO1), and glutathione S-transferase (GST) are important drug metabolizing enzymes. We aimed to elucidate the relationship between genetic polymorphisms of these enzymes and the susceptibility to DILI. METHODS: A total of 115 patients with DILI and 115 drug-, sex-, and age-matched controls were enrolled. Their genetic polymorphisms of MnSOD, NQO1, GSTM1, and GSTT1 were assayed. RESULTS: Sixty-three (54.8%) of DILI patients were incriminated to anti-tuberculosis drugs. Subjects with a mutant C allele (T/C or C/C genotype) of MnSOD had a higher risk of DILI than those with MnSOD T/T genotype, both in overall drugs studied (adjusted OR: 2.44, 95% C.I.: 1.38-4.30, P=0.002), and in sub-category of anti-tuberculosis drugs (adjusted OR: 2.47, 95% C.I.: 1.13-5.39, P=0.02). In addition, subjects carrying GSTM1 null genotype had increased risk of anti-tuberculosis DILI (adjusted OR: 2.23, 95% C.I.: 1.07-4.67, P=0.03). CONCLUSIONS: The MnSOD mutant C allele may increase the susceptibility to DILI, and GSTM1 null genotype may be related to anti-tuberculosis drug-induced hepatotoxicity. Determination of the MnSOD and GSTM1 genotypes may help identify patients at high risk for DILI. SN - 0168-8278 UR - https://www.unboundmedicine.com/medline/citation/17400324/Genetic_polymorphisms_of_manganese_superoxide_dismutase_NAD_P_H:quinone_oxidoreductase_glutathione_S_transferase_M1_and_T1_and_the_susceptibility_to_drug_induced_liver_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(07)00123-7 DB - PRIME DP - Unbound Medicine ER -