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

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 (<i>NAT2</i>) 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 <i>NAT2</i> 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 <i>NAT2</i> gene and discussion of their clinical applications, as well as the effect of <i>NAT2</i> 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 <i>NAT2</i> phenotyping approaches is discussed. The need for nationwide mapping of <i>NAT2</i> variants and the deployment of rapid, cost-effective genotyping platforms, especially in resource-limited endemic settings, are also emphasized. Moreover, how combining <i>NAT2</i> 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 <i>NAT2</i>-guided therapy in India's National TB Elimination Programme (NTEP) might change the dynamics of TB management in India.