NAT2 AND CYP2E1 POLYMORPHISMS AND ANTITUBERCULOSIS DRUGINDUCED HEPATOTOXICITY IN PERUVIAN PATIENTS

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 pr...

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Published in:	BAG. Journal of basic and applied genetics Vol. 33; p. 68
Main Authors:	Valverde, L J Jaramillo, Levano, K, Tarazona, D, Capristano, S, Zegarra-Chapoñan, R, Sánchez, C, Picardo, V Yufra, Tarazona-Santos, E, Ugarte-Gil, C, Chunga, H Guio
Format:	Journal Article
Language:	Spanish
Published:	Buenos Aires Sociedad Argentina de Genetica 01-12-2022
Subjects:	Acetyltransferase Cytochrome P450 Genotype & phenotype Hepatotoxicity Isoniazid Liver N-Acetyltransferase N-Acetyltransferase 2 Single-nucleotide polymorphism Tuberculosis
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Summary:	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 previous studies, we hypothesized that the interactions between slow CYP2E1 genotype and NAT2 slow acetylators will induce DILI in TB patients. In this cross-sectional study from 377 participants that completed their anti-TB treatment, we genotyped SNPs: rs1041983, rs1801280, rs1799929, rs1799930, rs1208 and rs1799931 for NAT2; rs3813867 and rs2031920 for CYP2E1. We found that rapid, intermediate, and slow NAT2 acetylator were present in 15%, 38% and 47% respectively of the general population. Intermediate NAT2 acetylator was 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. We propose that presence of NAT2 intermediate and CYP2E1 c1/c1 genotype could help in therapeutic drug monitoring, optimize its therapeutic benefits, while minimizing its risk for side effects or toxicity
ISSN:	1666-0390 1852-6233