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

• Published in: International journal of molecular sciences Vol. 22; no. 4; p. 1960
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.02.2021; MDPI
• Subjects: adverse drug reactions; Benznidazole; Brazil - epidemiology; Chagas disease; Chagas Disease - drug therapy; Chagas Disease - epidemiology; Chagas Disease - genetics; Chagas Disease - parasitology; Chromosome 16; Chromosomes; Dermatitis; Drug dosages; Evaluation; Female; Gene expression; Gene Regulatory Networks; Genome-Wide Association Study; Genomes; Genomic analysis; Genotype; Humans; Male; Middle Aged; Nitroimidazoles - adverse effects; Nucleotides; Pharmacogenomics; Polymorphism, Single Nucleotide; Prospective Studies; Public health; Risk; Signal transduction; Signal Transduction - genetics; Signs and symptoms; Single-nucleotide polymorphism; Transcription; Transcriptome; Transcriptomes; Tropical diseases; Trypanocidal Agents - adverse effects; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Brazil; Chagas disease; adverse drug reactions; pharmacogenomics; benznidazole
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22041960

Chagas disease remains a major social and public health problem in Latin America. Benznidazole (BZN) is the main drug with activity against . 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. 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 ( = 73), and those without ADRs ( = 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. 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 ( = 5.652 × 10 ). Transcriptomic data revealed three significantly enriched signaling pathways related to BZN ADRs. These data suggest that part of adverse BZN reactions might be genetically determined and may facilitate patient risk stratification prior to starting BZN treatment.