Bibliographic citations
Jaramillo, L., (2023). Polimorfismos de los genes enzimáticos NAT2, CYP2E1 y GST y presencia de reacción adversa a fármacos antituberculosos en la población peruana [Universidad Peruana Cayetano Heredia]. https://hdl.handle.net/20.500.12866/13310
Jaramillo, L., Polimorfismos de los genes enzimáticos NAT2, CYP2E1 y GST y presencia de reacción adversa a fármacos antituberculosos en la población peruana []. PE: Universidad Peruana Cayetano Heredia; 2023. https://hdl.handle.net/20.500.12866/13310
@phdthesis{renati/910643,
title = "Polimorfismos de los genes enzimáticos NAT2, CYP2E1 y GST y presencia de reacción adversa a fármacos antituberculosos en la población peruana",
author = "Jaramillo Valverde, Luis Jose",
publisher = "Universidad Peruana Cayetano Heredia",
year = "2023"
}
In Peru, 24,581 people were diagnosed with tuberculosis (TB) in 2020. Although TB treatment is effective, 3.4-13% is associated with adverse drug reactions (ADR), considering the Drug-Induced Liver Injury (DILI) as the most predominant in Peru. Among the first-line antituberculous medications, Isoniazide (INH) is the main cause of DILI's appearance. In the liver, INH is metabolized by the enzymes N- N-acetyltransferase -2 (NAT2) and the cytochrome P450 2E1 (CYP2E1) and Glutation S Transferase (GST) with two GSTT1 and GSTM1 isoforms. Little is known about whether the genetic characteristics of the patient infected with TB in Peru could be associated with the presence of adverse drug reactions. In the present study we explore with two research questions if the NAT2 acetylator phenotype, CYP2E1 genotype and the GST genotype with their two isoforms would be associated with the presence of adverse reactions in Peruvian patients infected with tuberculosis. Research 1: Transversal study that evaluated the interactions between the slow CYP2E1 genotype and the slow NAT2 acetylator and their association with the presence of DILI in patients with TB. 377 participants were evaluated and we found that the NAT2 intermediate acetylator is the least prevalent among patients with adverse reactions (p = 0.24). In addition, we report that the combination of NAT2 intermediate acetylator and the CYP2E1 C1/C1 genotype presents a weak protection association (OR = 0.13; p = 0.050) against the development of DILI in our population. Research 2: Transversal study that evaluated the interactions between GSTT1 and GSTM1 genotypes to associate with the presence of DILI in patients with TB. 377 participants were evaluated and we found that no genotype was prevailing in patients developed DILI. In addition, we report that the combination of the GSTM1 present genotype, null GSTT1 genotype, rapid NAT2 acetylator and CYP2E1 C1/C1 genotype had a significant risk for the development of DILI (OR = 11; p = 0.017) in our population. Therefore, we propose that the presence of NAT2 intermediate acetylator and C1/C1 genotype of CYP2E1 could help in drug therapeutic monitoring as it is a possible protective factor of the presence of DILI. In addition, that the presence of the GSTM1 wild genotype, null GSTT1 genotype, rapid NAT2 acetylator and CYP2E1 C1/C1 genotype in the study population could be considered as a risk factor for the development of RAM due to drug therapeutic intake.
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