Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole

Department 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, Brazil

Institute of Infectology Emílio Ribas, São Paulo 01246-900, Brazil

Blood Systems Research Institute, San Francisco, CA 94118, USA

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Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA

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Department of Genetics, Harvard Medical School, Boston, MA 02115, USA

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Laboratory of Genetics and Molecular Cardiology, The Heart Institute, University of São Paulo, São Paulo 05403-000, Brazil

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2021, 22(4), 1960; https://doi.org/10.3390/ijms22041960

Received: 14 November 2020 / Revised: 17 December 2020 / Accepted: 28 December 2020 / Published: 16 February 2021

(This article belongs to the Special Issue Genetic Analysis, Pathogenic Process Deciphering, Drug Development in Parasitic Diseases)

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Abstract

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. View Full-Text

Keywords: Chagas disease; benznidazole; adverse drug reactions; pharmacogenomics

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MDPI and ACS Style

Franco, L.A.M.; Moreira, C.H.V.; Buss, L.F.; Oliveira, L.C.; Martins, R.C.R.; Manuli, E.R.; Lindoso, J.A.L.; Busch, M.P.; Pereira, A.C.; Sabino, E.C. Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole. Int. J. Mol. Sci. 2021, 22, 1960. https://doi.org/10.3390/ijms22041960

AMA Style

Franco LAM, Moreira CHV, Buss LF, Oliveira LC, Martins RCR, Manuli ER, Lindoso JAL, Busch MP, Pereira AC, Sabino EC. Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole. International Journal of Molecular Sciences. 2021; 22(4):1960. https://doi.org/10.3390/ijms22041960

Chicago/Turabian Style

Franco, Lucas A.M., 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, and Ester C. Sabino. 2021. "Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole" International Journal of Molecular Sciences 22, no. 4: 1960. https://doi.org/10.3390/ijms22041960

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Pharmacogenomic Profile and Adverse Drug Reactions in a Prospective Therapeutic Cohort of Chagas Disease Patients Treated with Benznidazole

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