Genetic Polymorphisms of Cytochrome P450 and Glutathione S-transferase Associated with Antituberculosis Drug-induced Hepatotoxicity in Chinese Tuberculosis Patients

This study was designed to investigate the association of genetic polymorphisms of cytochrome P450 subtype 2E1 (CYP2E1) and glutathione S-transferase mu 1 (GSTM1) with susceptibility to antituberculosis drug-induced hepatotoxicity (ADIH) in Chinese tuberculosis patients. All patients were treated wi...

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Bibliographic Details
Published in:Journal of international medical research 2010-05, Vol.38 (3), p.977-986
Main Authors: Wang, T, Yu, HT, Wang, W, Pan, YY, He, LX, Wang, ZY
Format: Article
Language:English
Subjects:
Antitubercular Agents - adverse effects
Chemical and Drug Induced Liver Injury - enzymology
Chemical and Drug Induced Liver Injury - etiology
Chemical and Drug Induced Liver Injury - genetics
China
Cytochrome P-450 CYP2E1 - genetics
Cytochrome P-450 CYP2E1 - metabolism
Female
Glutathione Transferase - genetics
Glutathione Transferase - metabolism
Humans
Male
Middle Aged
Polymorphism, Genetic
Tuberculosis - drug therapy
Tuberculosis - enzymology
Tuberculosis - genetics
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Summary:This study was designed to investigate the association of genetic polymorphisms of cytochrome P450 subtype 2E1 (CYP2E1) and glutathione S-transferase mu 1 (GSTM1) with susceptibility to antituberculosis drug-induced hepatotoxicity (ADIH) in Chinese tuberculosis patients. All patients were treated with a combination of isoniazid, rifampicin, pyrazinamide and ethambutol. Genomic DNA from 104 patients with ADIH and 111 without ADIH was analysed for the frequency of CYP2E1 RsaI and GSTM1 RsaI genotypes by polymerase chain reaction and restriction fragment length polymorphism. The association of polymorphisms with susceptibility to ADIH was calculated using the χ2-test and logistic regression analysis. The CYP2E1 RsaI polymorphisms were significantly associated with ADIH and the c1/c1 genotype was an independent risk factor for ADIH. Compared with the GSTM1 RsaI present genotype, the GSTM1 RsaI null genotype tended to increase susceptibility to ADIH, but the association with ADIH was not significant. The results indicate that CYP2E1 RsaI genotype c1/c1 is a potential risk factor for ADIH in the Chinese population. The tendency of the GSTM1 RsaI null genotype to increase susceptibility to ADIH needs further study.
ISSN:0300-0605
1473-2300
DOI:10.1177/147323001003800324