Pharmacogenetic Study of Anti‐TB Drugs in the Native Ancestry 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 most prevalent. Limited data exist on genetic...
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Wiley
2025-06-01
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| Series: | Pharmacology Research & Perspectives |
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| Online Access: | https://doi.org/10.1002/prp2.70135 |
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| author | Luis Jaramillo‐Valverde Mary K. Horton Julio A. Poterico Cristina M. Lanata Heinner Guio |
| author_facet | Luis Jaramillo‐Valverde Mary K. Horton Julio A. Poterico Cristina M. Lanata Heinner Guio |
| author_sort | Luis Jaramillo‐Valverde |
| collection | DOAJ |
| description | 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 most prevalent. Limited data exist on genetic risk factors for DILI in Latin America; even less is known about these factors in native Peruvian 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 isoniazid, rifampin, ethambutol, and pyrazinamide, as identified in the PharmGKB database, were analyzed. Significant differences were 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 compared to those reported in the 1000 Genomes Project. These findings can inform the development of personalized therapeutic strategies to improve TB treatment outcomes among Peru's diverse subpopulations. |
| format | Article |
| id | doaj-art-b547ec04316843d893e08ac8061c1d36 |
| institution | DOAJ |
| issn | 2052-1707 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
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| series | Pharmacology Research & Perspectives |
| spelling | doaj-art-b547ec04316843d893e08ac8061c1d362025-08-20T03:21:31ZengWileyPharmacology Research & Perspectives2052-17072025-06-01133n/an/a10.1002/prp2.70135Pharmacogenetic Study of Anti‐TB Drugs in the Native Ancestry Peruvian PopulationLuis Jaramillo‐Valverde0Mary K. Horton1Julio A. Poterico2Cristina M. Lanata3Heinner Guio4INBIOMEDIC, Research and Technological Center Lima PeruNational Human Genome Research Institute, NIH Bethesda Maryland USAINBIOMEDIC, Research and Technological Center Lima PeruNational Human Genome Research Institute, NIH Bethesda Maryland USAINBIOMEDIC, Research and Technological Center Lima PeruABSTRACT 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 most prevalent. Limited data exist on genetic risk factors for DILI in Latin America; even less is known about these factors in native Peruvian 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 isoniazid, rifampin, ethambutol, and pyrazinamide, as identified in the PharmGKB database, were analyzed. Significant differences were 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 compared to those reported in the 1000 Genomes Project. These findings can inform the development of personalized therapeutic strategies to improve TB treatment outcomes among Peru's diverse subpopulations.https://doi.org/10.1002/prp2.70135genotypenative populationpharmacogeneticstuberculosis |
| spellingShingle | Luis Jaramillo‐Valverde Mary K. Horton Julio A. Poterico Cristina M. Lanata Heinner Guio Pharmacogenetic Study of Anti‐TB Drugs in the Native Ancestry Peruvian Population Pharmacology Research & Perspectives genotype native population pharmacogenetics tuberculosis |
| title | Pharmacogenetic Study of Anti‐TB Drugs in the Native Ancestry Peruvian Population |
| title_full | Pharmacogenetic Study of Anti‐TB Drugs in the Native Ancestry Peruvian Population |
| title_fullStr | Pharmacogenetic Study of Anti‐TB Drugs in the Native Ancestry Peruvian Population |
| title_full_unstemmed | Pharmacogenetic Study of Anti‐TB Drugs in the Native Ancestry Peruvian Population |
| title_short | Pharmacogenetic Study of Anti‐TB Drugs in the Native Ancestry Peruvian Population |
| title_sort | pharmacogenetic study of anti tb drugs in the native ancestry peruvian population |
| topic | genotype native population pharmacogenetics tuberculosis |
| url | https://doi.org/10.1002/prp2.70135 |
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