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
N1 - Funding Information:
The authors thank Shi-Yi Yang, MS, for his help in the determination of genotypes, and all attending physicians of the Division of Gastroenterology and Chest Department, Taipei Veterans General Hospital, for assistance in collecting patients and controls. This work is supported by grants from the Taipei Veterans General Hospital and the National Science Council of the Republic of China (91-2315-B-075-010 and 93-2314-B-075-068).
PY - 2007/7
Y1 - 2007/7
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.
AB - 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.
KW - Drug metabolizing enzyme
KW - Drug-induced liver injury
KW - Genetic polymorphism
KW - Glutathione S-transferase
KW - Manganese superoxide dismutase
KW - NAD(P)H:quinone oxidoreductase
KW - Toxic hepatitis
UR - http://www.scopus.com/inward/record.url?scp=34249284163&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2007.02.009
DO - 10.1016/j.jhep.2007.02.009
M3 - Article
C2 - 17400324
AN - SCOPUS:34249284163
SN - 0168-8278
VL - 47
SP - 128
EP - 134
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 1
ER -
