Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity

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Surendra K Sharma1, Brajesh Kumar Jha1, Abhishek Sharma1

  • 1Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.

The Indian Journal of Medical Research
|May 6, 2017
PubMed
Abstract

Insights

NAT2 gene polymorphism did not show a significant association with anti-tuberculosis drug-induced liver injury. However, specific NAT2 variants were more common in patients who developed liver injury.

Area of Science:

  • Pharmacogenomics
  • Genetics
  • Hepatology

Background:

  • The N-acetyltransferase 2 (NAT2) gene influences drug metabolism.
  • Polymorphisms in NAT2 may affect susceptibility to drug-induced liver injury (DIH).

Purpose of the Study:

  • To investigate the association between NAT2 gene polymorphism and anti-tuberculosis drug-induced hepatotoxicity (DIH).

Main Methods:

  • Prospective study comparing NAT2 genotypes using PCR-RFLP in 185 tuberculosis patients without DIH and 105 with DIH.
  • Analysis focused on slow-acetylator genotypes and specific variant distributions.

Main Results:

  • Slow-acetylator NAT2 genotype frequency was similar between DIH (82.8%) and non-DIH (77.2%) groups.
  • The NAT2*5/*7 variant genotype was significantly more prevalent in the DIH group (56%) versus non-DIH (39%) (OR 2.02, P=0.006).

Conclusions:

  • No overall association found between NAT2 genotype and DIH in North Indian tuberculosis patients.
  • Specific NAT2 variants may play a role, warranting further investigation.

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