Genetic polymorphisms and adverse reactions to antituberculosis therapy

Hannah M Gunter; Phuti Choshi; Tafadzwa Chimbetete; Sarah Pedretti; Rannakoe J Lehloenya; Phumla Z Sinxadi; Marylyn D Ritchie; Elizabeth J Phillips; David W Haas; Jonny G Peter

doi:10.1080/14622416.2025.2509479

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Genetic polymorphisms and adverse reactions to antituberculosis therapy

Journal article

Open access

Peer reviewed

Genetic polymorphisms and adverse reactions to antituberculosis therapy

Hannah M Gunter, Phuti Choshi, Tafadzwa Chimbetete, Sarah Pedretti, Rannakoe J Lehloenya, Phumla Z Sinxadi, Marylyn D Ritchie, Elizabeth J Phillips, David W Haas and Jonny G Peter

Pharmacogenomics, Vol.26(5-6), pp.207-221

2025

DOI: https://doi.org/10.1080/14622416.2025.2509479

PMID: 40538374

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Abstract

Antitubercular Agents - adverse effects

Antitubercular Agents - therapeutic use

Drug-Related Side Effects and Adverse Reactions - genetics

Humans

Pharmacogenetics - methods

Pharmacogenomic Testing - methods

Polymorphism, Genetic - genetics

Tuberculosis - drug therapy

Tuberculosis - genetics

Tuberculosis, Multidrug-Resistant - drug therapy

Tuberculosis, Multidrug-Resistant - genetics

Tuberculosis is the leading cause of death from a single infectious agent globally, with the highest burden in low-and middle-income countries. Successful treatment requires prolonged administration of multiple drugs. The increasing threat of multidrug-resistant tuberculosis has prompted the development of a robust pipeline for new drugs. While generally safe and well tolerated, adverse drug reactions (ADRs) to TB drugs have a considerable impact on treatment outcomes. Pharmacogenetic testing has been implemented for some diseases to identify at-risk individuals and prevent ADRs. For tuberculosis treatment, the use of pharmacogenetic testing to optimize complex regimens and avoid ADRs is appealing, but there has been minimal implementation. To improve the use of pharmacogenetics, understanding both the pharmacology of relevant drugs and population-specific pathophysiology of ADRs are essential. This review highlights the major treatment-limiting ADRs with TB drugs, the current understanding of drug metabolic pathways, ADR pathophysiology, and known pharmacogenetic risk alleles. We highlight research gaps and barriers to meaningful clinical use and implementation of pharmacogenomic testing to prevent adverse reactions to TB drugs.

Details

Title: Genetic polymorphisms and adverse reactions to antituberculosis therapy
Authors/Creators: Hannah M Gunter - Groote Schuur Hospital
Phuti Choshi - University of Cape Town
Tafadzwa Chimbetete - University of Cape Town
Sarah Pedretti - University of Cape Town
Rannakoe J Lehloenya - University of Cape Town
Phumla Z Sinxadi - Groote Schuur Hospital
Marylyn D Ritchie - California University of Pennsylvania
Elizabeth J Phillips - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
David W Haas - Vanderbilt University School of Medicine
Jonny G Peter - University of Cape Town
Publication Details: Pharmacogenomics, Vol.26(5-6), pp.207-221
Publisher: Informa UK Limited, trading as Taylor & Francis Group.
Grant note: R01 AI152183 / NIAID NIH HHS R01 AI077505 / NIAID NIH HHS P30 AI110527 / NIAID NIH HHS D43 TW010559 / FIC NIH HHS
Identifiers: 991005791873107891
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.117 Pharmacology & Toxicology; 1.117.1309 Drug-Induced Hepatotoxicity
Web Of Science research areas: Pharmacology & Pharmacy
ESI research areas: Pharmacology & Toxicology