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

Surendra K. Sharma, Brajesh Kumar Jha, Abhishek Sharma, V. Sreenivas, Vishwanath Upadhyay, Chandrita Jaisinghani, Rohit Singla, Hemant Kumar Mishra, Manish Soneja

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1 Scopus citations

Abstract

Background & objectives: The N-acetyltransferase 2 (NAT2) gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH). Methods: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. Results: Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8%) and non-DIH (77.2%) patients. However, the genotypic distribution of variant NAT2*5/*7 amongst slow-acetylator genotypes was significantly higher in DIH (56%) group as compared to non-DIH (39%) group (odds ratio 2.02; P=0.006). Interpretation & conclusions: The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.

Original languageEnglish (US)
Pages (from-to)924-928
Number of pages5
JournalIndian Journal of Medical Research
Volume144
Issue numberDECEMBER
DOIs
StatePublished - Dec 2016

Bibliographical note

Funding Information:
Authors thank the clinical, laboratory and administrative staff and patients of the AIIMS, New Delhi, for their support. This work was supported by the Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi (Grant number BT/PR7885/MED/14/1166/2006). The first author (SKS) was supported by JC Bose Fellowship [Department of Science and Technology, Ministry of Science and Technology, Government of India, New Delhi (No. SB/S2/JCB-04/2013)].

Publisher Copyright:
© 2017, Indian Council of Medical Research. All rights reserved.

Keywords

  • Drug-induced hepatotoxicity
  • Genetic polymorphism
  • N-acetyltransferase 2
  • Polymerase chain reaction
  • Rapid acetylator
  • Restriction fragment length polymorphism
  • Slow acetylator

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