A recent clinical trial used N-acetyltransferase 2 genotyping to determine the appropriate dose of isoniazid in an anti-tuberculosis therapeutic regimen and demonstrated that pharmacogenetic-based clinical algorithms have the potential to improve efficacy of a drug and to reduce DILI.
Among the patient-specific determinants of susceptibility to INH-associated DILI, the importance of HLA genetic variants has been increasingly recognized, whereas the role of polymorphisms of drug-metabolizing enzymes (NAT2 and CYP2E1) has become less important and remains controversial.
However, the combination of the CYP2E1 C1/C1 genotype with a slow acetylator NAT2 genotype increased the risk of anti-TB drug-induced hepatotoxicity (OR 5.33; P = 0.003) compared with the combination of a rapid acetylator NAT2 genotype with either a C1/C2 or C2/C2 genotype.5.
In conclusion, slow acetylator status of NAT2 was a significant susceptibility risk factor for antituberculosis drug-induced hepatotoxicity; NAT2 genotyping may be a useful tool for predicting antituberculosis drug-induced hepatotoxicity.
In conclusion, slow acetylator status of NAT2 was a significant susceptibility risk factor for antituberculosis drug-induced hepatotoxicity; NAT2 genotyping may be a useful tool for predicting antituberculosis drug-induced hepatotoxicity.
In conclusion, this study confirms the significance of the association between slow-acetylator NAT2 variants and susceptibility to AT-DILI in an Indonesian population.
Subset analysis of NAT2 acetylator status and severity grade confirmed these results in AT-DILI patients with more severe disease whereas fast and intermediate acetylator phenotypes were associated with a decreased AT-DILI risk.
The aim of this study is to evaluate the potential association between N-acetyltransferase type 2 (NAT2) polymorphisms and drug-induced liver injury during anti-TB treatment (AT-DILI).