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 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