NAT2 gene polymorphisms and plasma isoniazid concentration in Vietnamese tuberculosis patients

Abstract

Background: Isoniazid (INH) is one of the most common drug for tuberculosis (TB) treatment and INH acetylation catalysed by non-inducible hepatic enzyme arylamine N-acetyltransferase type 2 (NAT2). The isoniazid acetylation rates, which depends on NAT2 genotypes, is constant in an individual but can changes between patients. Phenotypic groups can be classified based on the genotype: slow, intermediate and rapid acetylators. This study was performed to identify the relation between NAT2 gene polymorphisms and plasma INH concentrations among the different genotypes of Vietnamese tuberculosis patients. Methods: Blood samples of 136 adult TB patients treated with INH were collected and genotyped for NAT2 gene polymorphisms using Sanger sequencing. Two-hour post-dosing INH plasma concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). Results: Among the 136 patients genotyped, there were 43 (31.62%), 58 (42.65%) and 35 (25.74%) of slow, intermediate and rapid acetylation phenotypes with two-hour post dosing INH plasma concentration of 3.4, 2.7 and 2.2 μg/ml, respectively. The differences in INH concentrations among the three genotypes were significant (P<0.05). Conclusions: Genotyping of TB patients from Vietnam for NAT2 gene polymorphism revealed that 48 per cent of the study population comprised slow acetylators. Two-hour INH levels were significantly different among slow and rapid acetylators.

Keywords

• N-acetyltransferase 2 enzyme
• NAT2 polymorphisms
• isoniazid
• tuberculosis