NAT2 Acetylation Phenotypes in India: A Narrative Review of Personalized TB Therapy

Abstract: Tuberculosis (TB) continues to be a significant health challenge in India, which necessitates accurate and personalized therapeutic strategies for its successful treatment. Polymorphisms in the N-acetyltransferase-2 ( NAT2 ) enzyme, involved in metabolism of a first-line drug, isoniazid (INH), for treatment of TB, have three acetylation phenotypes (slow, intermediate, or fast) that influence drug efficacy, toxicity and treatment outcomes. This article is presented as a narrative review of current research retrieved from PubMed, Scopus, and Google Scholar, focusing on studies related to NAT2 polymorphisms, pharmacogenomics, and tuberculosis therapy. The selected literature was reviewed to address the biological importance of the acetylation process and the development of DNA-based methods for genotyping of the NAT2 gene and discussion of their clinical applications, as well as the effect of NAT2 phenotypes on the treatment outcomes of TB. In addition, how highly genetic diversity in Indian populations necessitates the development of simplified and personalized medication therapy using population-based NAT2 phenotyping approaches is discussed. The need for nationwide mapping of NAT2 variants and the deployment of rapid, cost-effective genotyping platforms, especially in resource-limited endemic settings, are also emphasized. Moreover, how combining NAT2 profiling with additional pharmacogenetic markers may lead to a comprehensive framework for TB treatment optimization is also discussed. It is envisioned that integration of all of these approaches under NAT2 -guided therapy in India’s National TB Elimination Programme (NTEP) might change the dynamics of TB management in India. Keywords: tuberculosis, NAT2 genetic polymorphisms, pharmacogenomics, personalized medicine