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CYP2E1, GSTM1 and GSTT1 genetic polymorphisms and susceptibility to antituberculosis drug-induced hepatotoxicity: a

S-W Tang1, X-Z Lv, Y Zhang

  • 1Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.

Journal of Clinical Pharmacy and Therapeutics
|February 17, 2012
PubMed
Abstract

Insights

Genetic variations in drug-metabolizing enzymes like CYP2E1, GSTM1, and GSTT1 were not associated with antituberculosis drug-induced hepatotoxicity (ATDH) in a Chinese population. This prospective study found no significant links, challenging previous findings.

Area of Science:

  • Pharmacogenomics
  • Hepatotoxicity Research
  • Tuberculosis Treatment

Background:

  • Antituberculosis drug-induced hepatotoxicity (ATDH) is a significant concern.
  • Genetic polymorphisms in drug-metabolizing enzymes (CYP2E1, GSTM1, GSTT1) are implicated, but findings are inconsistent.
  • Previous studies were often hospital-based and retrospective.

Purpose of the Study:

  • To investigate the association between CYP2E1, GSTM1, and GSTT1 genetic polymorphisms and ATDH.
  • To utilize a robust, population-based prospective cohort design for increased reliability.
  • To clarify conflicting previous research on genetic risk factors for ATDH.

Main Methods:

  • A prospective cohort of 4304 tuberculosis patients was monitored for 6-9 months.
  • A nested case-control study with 89 ATDH cases and 356 controls was conducted.
  • CYP2E1, GSTM1, and GSTT1 polymorphisms were genotyped using PCR-RFLP and multiplex PCR.
  • Conditional logistic regression analyzed associations (OR, 95% CI).

Main Results:

  • No statistically significant association was found between CYP2E1 RsaI or DraI genotypes and ATDH.
  • No significant association was observed between GSTM1/GSTT1 null genotypes and ATDH.
  • Odds ratios and confidence intervals did not indicate a risk conferred by these specific genetic polymorphisms.

Conclusions:

  • This is the first prospective, population-based nested case-control study on these genetic polymorphisms and ATDH.
  • The study could not confirm associations between CYP2E1, GSTM1, or GSTT1 genetic polymorphisms and ATDH in the studied Chinese population.
  • Findings challenge previous reports suggesting a role for these genetic variations in ATDH.

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