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

• Published in: Journal of hepatology Vol. 47; no. 1; pp. 128 - 134
• Main Authors: Huang, Yi-Shin, Su, Wei-Juin, Huang, Yi-Hsiang, Chen, Chih-Yen, Chang, Full-Young, Lin, Han-Chieh, Lee, Shou-Dong
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.07.2007; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Antitubercular Agents - toxicity; Bacterial diseases; Biological and medical sciences; Chemical and Drug Induced Liver Injury - genetics; Drug metabolizing enzyme; Drug toxicity and drugs side effects treatment; Drug-induced liver injury; Drug-Related Side Effects and Adverse Reactions; Female; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Genetic polymorphism; Genetic Predisposition to Disease; Glutathione S-transferase; Glutathione Transferase - genetics; Human bacterial diseases; Humans; Infectious diseases; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Manganese superoxide dismutase; Medical sciences; Middle Aged; Mutation; NAD(P)H Dehydrogenase (Quinone) - genetics; NAD(P)H:quinone oxidoreductase; Other diseases. Semiology; Pharmacology. Drug treatments; Polymorphism, Genetic; Superoxide Dismutase - genetics; Toxic hepatitis; Toxicity: digestive system; Tuberculosis and atypical mycobacterial infections; Drug metabolizing enzyme; Genetic polymorphism; Drug-induced liver injury; Toxic hepatitis; Glutathione S-transferase; Manganese superoxide dismutase; NAD(P)H:quinone oxidoreductase; Enzyme; Transferases; Hepatic disease; Superoxide dismutase; Mycobacterial infection; Infection; Hepatitis; Tuberculosis; Glutathione transferase; Drug- induced liver injury; Bacteriosis; Digestive diseases; Genetics; Oxidoreductases; Hepatotoxicity; Manganese; Polymorphism
• DOI: 10.1016/j.jhep.2007.02.009
• ISSN: 0168-8278

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. 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. 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). 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.