Comparison between acetylator phenotype and genotype polymorphism of n-acetyltransferase-2 in tuberculosis patients

Abstract

Isoniazid (INH) is one of the most important drugs of antitubercular treatment regime, and in some cases it causes hepatotoxicity. It is metabolized by hepatic N-acetyltransferase-2 (NAT2). To compare whether both methods, i.e., genotype NAT2 and phenotype test of measuring serum INH levels, are useful to identify acetylator status of patients on antitubercular treatment (ATT). A total of 251 tuberculosis (TB) patients on standard treatment were followed up to 6months for this study. NAT2 genotype was assessed by PCR with restriction fragment length polymorphism (RFLP) whereas serum INH levels were measured by fluorometry. Of the 251 patients, 50 (19.9%) developed ATT-induced hepatotoxicity. By phenotypic estimation, in the hepatotoxicity group, 17/50 (34%) were slow acetylators whereas 33/50 (66%) were fast acetylators. Genotypically, 19/50 (38%) were slow acetylators and 31/50 (62%) fast acetylators. By phenotypic analysis, in non-hepatotoxicity group, 46/201 (22.9%) were slow acetylators and 155/201 (77.1%) fast acetylators. By genotypic analysis, 30/201 (14.9%) were slow acetylators and 171/201 (85%) fast acetylators. Overall, slow acetylators (25.1%) measured phenotypically were not significantly different from slow acetylators (19.5%) measured genotypically. This study suggests that the acetylator status of TB patients can be detected by phenotypic method as efficaciously as by genotypic method. Therefore, phenotypic method can replace genotypic method to determine acetylating status as phenotypic method is simple and inexpensive.