Pharmacogenetic Study of Anti-TB Drugs in the NativeAncestry Peruvian Population

Abstract

In Peru, 33 113 individuals were diagnosed with tuberculosis (TB) in 2023. While TB treatments are generally effective, 3.4%to 13% of cases are associated with significant adverse drug reactions, with drug-induced liver injury (DILI) being the mostprevalent. Limited data exist on genetic risk factors for DILI in Latin America; even less is known about these factors in nativePeruvian populations. This study aimed to determine the prevalence of TB drug-metabolizing genotypes in these populations.A cross-sectional analysis was conducted using genetic data from 254 participants from the Peruvian Genome Project (PGP)representing three subpopulations: Coast, Andes, and Amazon. Twenty-three genes associated with TB treatment, include isoni-azid, rifampin, ethambutol, and pyrazinamide, as identified in the PharmGKB database, were analyzed. Significant differenceswere observed in genotype frequencies among subpopulations for AGBL4, NAT2, GSTP1, SLCO1B1, NOS, and CYP2B6 genes.The Amazonian population demonstrated a higher risk of DILI due to the increased prevalence of hepatotoxic alleles in AGBL4,GSTP1, and SLCO1B1. In contrast, alleles in the NOS gene indicated a lower risk of hepatotoxicity in the Andean population.However, the high-risk genotypes identified in the study's native Peruvian populations exhibit distinct prevalence patterns com-pared to those reported in the 1000 Genomes Project. These findings can inform the development of personalized therapeuticstrategies to improve TB treatment outcomes among Peru's diverse subpopulations.