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.
OBJECTIVE
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.
Huang
Yi-Shin
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
Wei-Juin
WJ
Huang
Yi-Hsiang
YH
Chen
Chih-Yen
CY
Chang
Full-Young
FY
Lin
Han-Chieh
HC
Lee
Shou-Dong
SD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000995:Antitubercular Agents / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D011110:Polymorphism, Genetic; D013482:Superoxide Dismutase / Q000235:genetics*
D000995:Antitubercular Agents; D005982:Glutathione Transferase; D016660:NAD(P)H Dehydrogenase (Quinone); D013482:Superoxide Dismutase; C447479:NQO1 protein, human; C413545:glutathione S-transferase T1