Universidad Peruana Cayetano Heredia

NAT2 and CYP2E1 polymorphisms and antituberculosis drug-induced hepatotoxicity in Peruvian patients

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dc.contributor.author Jaramillo-Valverde, Luis
dc.contributor.author Levano, Kelly S.
dc.contributor.author Tarazona, David D.
dc.contributor.author Capristano, Silvia
dc.contributor.author Zegarra-Chaponan, Roberto
dc.contributor.author Sanchez, Cesar
dc.contributor.author Yufra-Picardo, Velia M.
dc.contributor.author Tarazona-Santos, Eduardo
dc.contributor.author Ugarte Gil, Cesar Augusto
dc.contributor.author Guio, Heinner
dc.date.accessioned 2022-08-15T20:11:08Z
dc.date.available 2022-08-15T20:11:08Z
dc.date.issued 2022
dc.identifier.uri https://hdl.handle.net/20.500.12866/12025
dc.description.abstract Background: In Peru, 32,970 people were diagnosed with tuberculosis (TB) in 2019. Although TB treatment is effective, 3.4%–13% is associated with significant adverse drug reactions (ADR), considering drug-induced liver injury (DILI) as the most prevalent. Among the first-line anti-TB drugs, isoniazid (INH) is primarily responsible for the occurrence of DILI. INH is metabolized in the liver by the enzymes N-acetyltransferase-2 (NAT2) and Cytochrome P450 2E1 (CYP2E1). Based on the previous studies, we hypothesized that the interactions between slow CYP2E1 genotype and NAT2 slow acetylators will induce DILI in TB patients. Methods: In this cross-sectional study, all 377 participants completed their anti-TB treatment, and we genotyped SNPs: rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931 for NAT2 and rs3813867 and rs2031920 for CYP2E1. Results: We found that rapid, intermediate, and slow NAT2 acetylator were 15%, 38%, and 47%, respectively, in the general population. Intermediate NAT2 acetylator is the least prevalent among patients with adverse reactions (p = 0.024). We did not confirm our hypothesis, however, we found that the combination of intermediate NAT2 acetylators and CYP2E1 c1/c1 genotype significantly protected (OR = 0.16; p = 0.049) against the development of DILI in our population. Conclusion: We propose that the presence of NAT2 intermediate and CYP2E1 c1/c1 genotype could help in therapeutic drug monitoring, and optimize its therapeutic benefits while minimizing its risk for side effects or toxicity. en_US
dc.description.sponsorship Este trabajo fue financiado por FONDECYT/CIENCIACTIVA en el marco del programa de Investigación Epidemiológica de la Universidad Peruana Cayetano Heredia [beca EF033-235-2015]. es_PE
dc.language.iso eng
dc.publisher Wiley
dc.relation.ispartofseries Molecular Genetics & Genomic Medicine
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject CYP2E1 en_US
dc.subject Hepatotoxicity en_US
dc.subject NAT2 en_US
dc.subject Tuberculosis en_US
dc.title NAT2 and CYP2E1 polymorphisms and antituberculosis drug-induced hepatotoxicity in Peruvian patients en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1002/mgg3.1987
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.07
dc.relation.issn 2324-9269


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