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 <i>Trypanosoma cruzi</i>. Due to the high number of adverse drug reactions (ADRs), BZN is underprescribed. The goal of this study was to evaluate th...
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/1960 |
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| author | Lucas A. M. Franco Carlos H. V. Moreira Lewis F. Buss Lea C. Oliveira Roberta C. R. Martins Erika R. Manuli José A. L. Lindoso Michael P. Busch Alexandre C. Pereira Ester C. Sabino |
| author_facet | Lucas A. M. Franco Carlos H. V. Moreira Lewis F. Buss Lea C. Oliveira Roberta C. R. Martins Erika R. Manuli José A. L. Lindoso Michael P. Busch Alexandre C. Pereira Ester C. Sabino |
| author_sort | Lucas A. M. Franco |
| collection | DOAJ |
| description | Chagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against <i>Trypanosoma cruzi</i>. 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 (<i>n</i> = 73), and those without ADRs (<i>n</i> = 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 (<i>p</i> = 5.652 × 10<sup>−8</sup>). 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. |
| first_indexed | 2024-03-09T00:49:16Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:49:16Z |
| publishDate | 2021-02-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1ef63e1acfdd41c4a34e6264eb5790412023-12-11T17:17:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224196010.3390/ijms22041960Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with BenznidazoleLucas A. M. Franco0Carlos H. V. Moreira1Lewis F. Buss2Lea C. Oliveira3Roberta C. R. Martins4Erika R. Manuli5José A. L. Lindoso6Michael P. Busch7Alexandre C. Pereira8Ester C. Sabino9Department of Infectious Disease and Institute of Tropical Medicine (IMT-SP), University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 470, São Paulo 05403-000, BrazilDepartment of Infectious Disease and Institute of Tropical Medicine (IMT-SP), University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 470, São Paulo 05403-000, BrazilDepartment of Infectious Disease and Institute of Tropical Medicine (IMT-SP), University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 470, São Paulo 05403-000, BrazilDepartment of Infectious Disease and Institute of Tropical Medicine (IMT-SP), University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 470, São Paulo 05403-000, BrazilDepartment of Infectious Disease and Institute of Tropical Medicine (IMT-SP), University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 470, São Paulo 05403-000, BrazilDepartment of Infectious Disease and Institute of Tropical Medicine (IMT-SP), University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 470, São Paulo 05403-000, BrazilInstitute of Infectology Emílio Ribas, São Paulo 01246-900, BrazilBlood Systems Research Institute, San Francisco, CA 94118, USADepartment of Genetics, Harvard Medical School, Boston, MA 02115, USADepartment of Infectious Disease and Institute of Tropical Medicine (IMT-SP), University of São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 470, São Paulo 05403-000, BrazilChagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against <i>Trypanosoma cruzi</i>. 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 (<i>n</i> = 73), and those without ADRs (<i>n</i> = 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 (<i>p</i> = 5.652 × 10<sup>−8</sup>). 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.https://www.mdpi.com/1422-0067/22/4/1960Chagas diseasebenznidazoleadverse drug reactionspharmacogenomics |
| spellingShingle | Lucas A. M. Franco Carlos H. V. Moreira Lewis F. Buss Lea C. Oliveira Roberta C. R. Martins Erika R. Manuli José A. L. Lindoso Michael P. Busch Alexandre C. Pereira Ester C. Sabino Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole International Journal of Molecular Sciences Chagas disease benznidazole adverse drug reactions pharmacogenomics |
| 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 | Chagas disease benznidazole adverse drug reactions pharmacogenomics |
| url | https://www.mdpi.com/1422-0067/22/4/1960 |
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