[The effect of GST M1 and GST T1 gene mutations on anti-tuberculous drug induced hepatic injury]

Zhonghua Jie He He Hu Xi Za Zhi. 2009 Apr;32(4):266-9.
[Article in Chinese]

Abstract

Objective: To study the relationship between the polymorphisms of GST M1 and GST T1 genes and anti-tuberculous drug induced hepatic injury (ADIH).

Methods: A 1:1 matched case-control study was carried out. One hundred and six patients [age (49 +/- 19) years, 73 men and 33 women] fulfilling the criteria of ADIH during the 3 month follow-up after the initiation of anti-tuberculous therapy were included, while 106 cases [age (49 +/- 19) years, 73 men and 33 women] without any hepatic injury served as the controls. The genotypes of GST M1 and GST T1 genetic polymorphisms were detected by polymerase chain reaction (PCR) in patients who received anti-tuberculosis therapy. Using SPSS 11.5 for windows software, univariate and multivariate conditional logistic analyses were conducted for studying the relationship between the polymorphisms and ADIH.

Results: Univariate analysis demonstrated that the "null" genotype of GST M1 gene occurred in 50 (47.2%) of the cases, more frequent than in the controls [25 (23.6%)], with a crude OR (95%CI) 2.786 (1.513 - 5.130). No significant association was observed between ADIH and GST T1 polymorphism. Among the risk factors analyzed, body mass index and alcohol drinking were significantly associated with ADIH. In the multivariate analysis, a significant association between ADIH and the "null" genotype of GST M1 existed, after adjusting for body mass index and drinking status, adjusted OR (95%CI) being 3.022 (1.540 - 5.926). Again, no significant association was observed between GST T1 polymorphism and ADIH.

Conclusion: This study demonstrated that patients carrying GST M1-"null" genotype may be susceptible to ADIH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antitubercular Agents / adverse effects*
  • Case-Control Studies
  • Chemical and Drug Induced Liver Injury, Chronic / genetics*
  • Female
  • Follow-Up Studies
  • Genotype
  • Glutathione Transferase / genetics*
  • Humans
  • Liver / pathology
  • Male
  • Middle Aged
  • Mutation
  • Polymorphism, Genetic*
  • Young Adult

Substances

  • Antitubercular Agents
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1