Observational studyPharmacogenetics and genomics2025
Pharmacogenetics of tuberculosis treatment toxicity and effectiveness in a large Brazilian cohort.
Observational study in Pharmacogenetics and genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Regimen-Specific Population Pharmacokinetics of Isoniazid with and Without Rifamycin: A Bayesian Modeling Analysis of 6H, 3HR, and 3H2P2 Regimens.Pharmaceutics · 2026Article
- Genetic ancestry proportion influences risk of adverse events from tuberculosis treatment in Brazil.Human genetics · 2026Observational
- Genomics in Health and Biomedicine.Advances in experimental medicine and biology · 2026Review
- Cost-utility analysis of stratified isoniazid dosing by NAT2 genotype compared with isoniazid standard regimen for new patients with pulmonary tuberculosis in Thailand.Frontiers in public health · 2026Article
- Implementing health economics for pharmacogenomics research translation in Africa.Communications medicine · 2025Review
- Pharmacogenomics of antibiotic-induced hypersensitivity reactions: current evidence and implications in clinical practice.Frontiers in pharmacology · 2025Review
- Genetic Variations and Antibiotic-Related Adverse Events.Pharmaceuticals (Basel, Switzerland) · 2024Review
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14 authors.
Funding
Abstract
backgroundGenetic polymorphisms have been associated with risk of antituberculosis treatment toxicity. We characterized associations with adverse events and treatment failure/recurrence among adults treated for tuberculosis in Brazil.
methodsParticipants were followed in Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil. We included persons with culture-confirmed drug-susceptible pulmonary tuberculosis who started treatment between 2015 and 2019, and who were eligible for pharmacogenetics. Treatment included 2 months of isoniazid, rifampin or rifabutin, pyrazinamide, and ethambutol, then 4 months of isoniazid and rifampin or rifabutin, with 24-month follow-up. Analyses included 43 polymorphisms in 20 genes related to antituberculosis drug hepatotoxicity or pharmacokinetics. Whole exome sequencing was done in a case-control toxicity subset.
resultsAmong 903 participants in multivariable genetic association analyses, NAT2 slow acetylator status was associated with increased risk of treatment-related grade 2 or greater adverse events, including hepatotoxicity. Treatment failure/recurrence was more likely among NAT2 rapid acetylators, but not statistically significant at the 5% level. A GSTM1 polymorphism (rs412543) was associated with increased risk of treatment-related adverse events, including hepatotoxicity. SLCO1B1 polymorphisms were associated with increased risk of treatment-related hepatoxicity and treatment failure/recurrence. Polymorphisms in NR1/2 were associated with decreased risk of adverse events and increased risk of failure/recurrence. In whole exome sequencing, hepatotoxicity was associated with a polymorphism in VTI1A , and the genes METTL17 and PRSS57 , but none achieved genome-wide significance.
conclusionIn a clinical cohort representing three regions of Brazil, NAT2 acetylator status was associated with risk for treatment-related adverse events. Additional significant polymorphisms merit investigation in larger study populations, particularly regarding risk of treatment failure/recurrence.
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