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GSTT1 and GSTM1 null mutations and adverse reactions induced by antituberculosis drugs in Koreans

Sang-Heon Kim1, Sang-Hoon Kim, Ho Joo Yoon

  • 1Department of Internal Medicine, Hanyang University College of Medicine, Haengdang-dong 17, Seongdong-gu, Seoul 133-792, Korea. sangheonkim@hanyang.ac.kr <sangheonkim@hanyang.ac.kr>

Tuberculosis (Edinburgh, Scotland)
|December 29, 2009
PubMed

Insights

Glutathione S-transferase (GST) enzyme null mutations in GSTT1 and GSTM1 genes were not linked to antituberculosis drug (ATD)-induced hepatitis or skin reactions in a Korean population. These findings suggest GST enzymes do not significantly contribute to these adverse drug reactions.

Area of Science:

  • Pharmacogenomics
  • Toxicology
  • Drug Metabolism

Background:

  • Adverse reactions to antituberculosis drugs (ATD) can lead to severe illness and treatment interruptions.
  • Glutathione S-transferase (GST) enzymes are hypothesized to protect against ATD toxicity by detoxifying reactive metabolites.
  • Null mutations in GST genes, specifically GSTT1 and GSTM1, may alter an individual's susceptibility to ATD-induced adverse reactions.

Purpose of the Study:

  • To investigate the association between null mutations in GSTT1 and GSTM1 genes and the development of ATD-induced hepatitis and cutaneous reactions.
  • To determine if GST enzyme deficiencies play a role in the pathogenesis of specific ATD adverse events.

Main Methods:

  • A case-control study was conducted comparing the frequencies of GSTT1 and GSTM1 null mutations.
  • Genotyping for GSTT1 and GSTM1 null mutations was performed in 57 patients with ATD-induced hepatitis, 94 patients with ATD-induced cutaneous reactions, and 190 ATD-tolerant controls.
  • Statistical analysis was used to compare mutation frequencies between patient groups and controls.

Main Results:

  • No significant difference was found in the frequency of GSTT1 null mutations between patients with ATD-induced hepatitis (59.6%) and controls (54.2%).
  • Similarly, GSTM1 null mutation frequencies did not differ significantly between hepatitis patients (45.6%) and controls (54.7%).
  • Frequencies of both GSTT1 and GSTM1 null mutations were also not significantly different in patients with ATD-induced cutaneous reactions compared to controls.

Conclusions:

  • GSTT1 and GSTM1 null mutations are not associated with an increased risk of developing ATD-induced hepatitis or cutaneous reactions in the studied Korean population.
  • The findings suggest that glutathione S-transferase enzymes may not play a critical role in the mechanisms underlying these specific antituberculosis drug adverse reactions.

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