Influence of N-acetyltransferase 2 polymorphisms and clinical variables on liver function profile of tuberculosis patients

Levin Thomas, Arun Prasath Raju, S. Chaithra, Shrivathsa Kulavalli, Muralidhar Varma, Chidananda Sanju SV, Mithu Baneerjee, Kavitha Saravu, Surulivelrajan Mallayasamy, Mahadev Rao

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Single nucleotide polymorphisms (SNPs) in the N-acetyltransferase 2 (NAT2) gene as well as several other clinical factors can contribute to the elevation of liver function test values in tuberculosis (TB) patients receiving antitubercular therapy (ATT). Research design and methods: A prospective study involving dynamic monitoring of the liver function tests among 130 TB patients from baseline to 98 days post ATT initiation was undertaken to assess the influence of pharmacogenomic and clinical variables on the elevation of liver function test values. Genomic DNA was extracted from serum samples for the assessment of NAT2 SNPs. Further, within this study population, we conducted a case control study to identify the odds of developing ATT-induced drug-induced liver injury (DILI) based on NAT2 SNPs, genotype and phenotype, and clinical variables. Results: NAT2 slow acetylators had higher mean [90%CI] liver function test values for 8–28 days post ATT and higher odds of developing DILI (OR: 2.73, 90%CI: 1.05–7.09) than intermediate acetylators/rapid acetylators. Conclusion: The current study findings provide evidence for closer monitoring among TB patients with specific NAT2 SNPs, genotype and phenotype, and clinical variables, particularly between the period of more than a week to one-month post ATT initiation for better treatment outcomes.

Original languageEnglish
Pages (from-to)263-274
Number of pages12
JournalExpert Review of Clinical Pharmacology
Volume17
Issue number3
DOIs
Publication statusPublished - 2024

All Science Journal Classification (ASJC) codes

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

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