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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.

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Authors+Show Affiliations

Huang YS
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.tw
Su WJ
No affiliation info available
Huang YH
No affiliation info available
Chen CY
No affiliation info available
Chang FY
No affiliation info available
Lin HC
No affiliation info available
Lee SD
No affiliation info available

MeSH

AdultAgedAged, 80 and overAllelesAntitubercular AgentsChemical and Drug Induced Liver InjuryDrug-Related Side Effects and Adverse ReactionsFemaleGenetic Predisposition to DiseaseGlutathione TransferaseHumansMaleMiddle AgedMutationNAD(P)H Dehydrogenase (Quinone)Polymorphism, GeneticSuperoxide Dismutase

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 -