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Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole
Chagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against Trypanosoma cruzi. Due to the high number of adverse drug reactions (ADRs), BZN is underprescribed. The goal of this study was to evaluate the genetic and trans...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920452/ https://www.ncbi.nlm.nih.gov/pubmed/33669428 http://dx.doi.org/10.3390/ijms22041960 |
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author | Franco, Lucas A. M. Moreira, Carlos H. V. Buss, Lewis F. Oliveira, Lea C. Martins, Roberta C. R. Manuli, Erika R. Lindoso, José A. L. Busch, Michael P. Pereira, Alexandre C. Sabino, Ester C. |
author_facet | Franco, Lucas A. M. Moreira, Carlos H. V. Buss, Lewis F. Oliveira, Lea C. Martins, Roberta C. R. Manuli, Erika R. Lindoso, José A. L. Busch, Michael P. Pereira, Alexandre C. Sabino, Ester C. |
author_sort | Franco, Lucas A. M. |
collection | PubMed |
description | Chagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against Trypanosoma cruzi. Due to the high number of adverse drug reactions (ADRs), BZN is underprescribed. The goal of this study was to evaluate the genetic and transcriptional basis of BZN adverse reactions. Methods: A prospective cohort with 102 Chagas disease patients who underwent BZN treatment was established to identify ADRs and understand their genetic basis. The patients were classified into two groups: those with at least one ADR (n = 73), and those without ADRs (n = 29). Genomic analyses were performed comparing single nucleotide polymorphisms between groups. Transcriptome data were obtained comparing groups before and after treatment, and signaling pathways related to the main ADRs were evaluated. Results: A total of 73 subjects (71.5%) experienced ADRs. Dermatological symptoms were most frequent (45.1%). One region of chromosome 16, at the gene LOC102724084 (rs1518601, rs11861761, and rs34091595), was associated with ADRs (p = 5.652 × 10(−8)). Transcriptomic data revealed three significantly enriched signaling pathways related to BZN ADRs. Conclusions: These data suggest that part of adverse BZN reactions might be genetically determined and may facilitate patient risk stratification prior to starting BZN treatment. |
format | Online Article Text |
id | pubmed-7920452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79204522021-03-02 Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole Franco, Lucas A. M. Moreira, Carlos H. V. Buss, Lewis F. Oliveira, Lea C. Martins, Roberta C. R. Manuli, Erika R. Lindoso, José A. L. Busch, Michael P. Pereira, Alexandre C. Sabino, Ester C. Int J Mol Sci Article Chagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against Trypanosoma cruzi. Due to the high number of adverse drug reactions (ADRs), BZN is underprescribed. The goal of this study was to evaluate the genetic and transcriptional basis of BZN adverse reactions. Methods: A prospective cohort with 102 Chagas disease patients who underwent BZN treatment was established to identify ADRs and understand their genetic basis. The patients were classified into two groups: those with at least one ADR (n = 73), and those without ADRs (n = 29). Genomic analyses were performed comparing single nucleotide polymorphisms between groups. Transcriptome data were obtained comparing groups before and after treatment, and signaling pathways related to the main ADRs were evaluated. Results: A total of 73 subjects (71.5%) experienced ADRs. Dermatological symptoms were most frequent (45.1%). One region of chromosome 16, at the gene LOC102724084 (rs1518601, rs11861761, and rs34091595), was associated with ADRs (p = 5.652 × 10(−8)). Transcriptomic data revealed three significantly enriched signaling pathways related to BZN ADRs. Conclusions: These data suggest that part of adverse BZN reactions might be genetically determined and may facilitate patient risk stratification prior to starting BZN treatment. MDPI 2021-02-16 /pmc/articles/PMC7920452/ /pubmed/33669428 http://dx.doi.org/10.3390/ijms22041960 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Franco, Lucas A. M. Moreira, Carlos H. V. Buss, Lewis F. Oliveira, Lea C. Martins, Roberta C. R. Manuli, Erika R. Lindoso, José A. L. Busch, Michael P. Pereira, Alexandre C. Sabino, Ester C. Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole |
title | Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole |
title_full | Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole |
title_fullStr | Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole |
title_full_unstemmed | Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole |
title_short | Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole |
title_sort | pharmacogenomic profile and adverse drug reactions in a prospective therapeutic cohort of chagas disease patients treated with benznidazole |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920452/ https://www.ncbi.nlm.nih.gov/pubmed/33669428 http://dx.doi.org/10.3390/ijms22041960 |
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