Determination of NAT2 Genotypes in a Cohort of Patients with Suspected TB in the State of Rio de Janeiro

TL;DR

This study analyzed the NAT2 gene in tuberculosis patients in Rio de Janeiro to understand how genetic differences affect drug metabolism and treatment outcomes.

Contribution

The study provides new insights into NAT2 genotype frequencies and acetylation phenotypes in a TB patient cohort in Brazil.

Findings

The NAT2*5B allele was the most frequent in the studied population.

47.9% of individuals exhibited a slow acetylation phenotype.

Pharmacogenetic analysis could improve TB treatment outcomes and reduce drug resistance.

Abstract

The human N-acetyltransferase 2 enzyme, encoded by the NAT2 gene, plays an important role in the metabolism of isoniazid, the main drug used to treat tuberculosis. The interindividual variation in the response of patients to drug treatment for tuberculosis may be responsible for the occurrence of unfavorable outcomes. The presence of polymorphisms in genes associated with the metabolism and transport of drugs, receptors, and therapeutic targets has been identified as a major determinant of this variability. The objective of this study was to identify the genetic profile of NAT2 in the study population. Using the obtained genomic DNA followed by PCR amplification and sequencing, the frequency of nine SNPs as well as alleles associated with slow (47.9%), intermediate (38.7%), and fast acetylation phenotypes (11.3%), in addition to those whose phenotype has not yet been characterized (2.1%), was estimated. The NAT2*5B allele was identified more frequently (31.3%). The description of SNPs in pharmacogenes and the establishment of their relationship with the pharmacokinetics of an individual offer an individualized approach that allows us to reduce the unfavorable outcomes of a therapy, ensure better adherence to treatment, prevent the emergence of MDR strains, reduce the cost of treatment, and improve the quality of patients’ lives.