title: Correlation of N-acetyltransferase 2 genotype with isoniazid acetylation in Polish tuberculosis patients.
abstract: Isoniazid (INH), a key agent in the treatment of tuberculosis (TB), is metabolized primarily by the genetically polymorphic N-acetyltransferase 2 (NAT2) enzyme. Patients treated with INH can be classified as fast, intermediate, and slow acetylators. The objective of this study was to explore the relationship between NAT2 genotypes and the serum concentrations of INH. Blood samples from 130 patients were taken for the analysis, and plasma INH concentrations were determined by using the high-performance liquid chromatography (HPLC) technology. Acetylation genotype was determined on genomic DNA by using an allele-specific polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Once the NAT2 genotypes were established, patients were classified into three categories: fast, intermediate, and slow acetylators. Of the 130 patients studied, 84 (64.6%) were slow, 39 (30%) were intermediate, and 7 (5.4%) were fast acetylators. Analysis of INH concentrations in the blood of patients receiving the approximate doses of the drug revealed that, at the time intervals examined, the average concentration of INH was 2- to 7-fold higher among slow acetylators compared to fast and intermediate acetylators.
  
  
  CONCLUSIONS
  Determining mutations in the NAT2 gene enabled the identification of the INH acetylation type in patients and the genotyping results were consistent with the phenotype determined by methods of measurement of drug bioavailability.
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, 01-138 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Zabost
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, 01-138 Warsaw, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Brzezińska
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, 01-138 Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Kozińska
authors.affiliation: Mazovian Center for Lung Diseases and Tuberculosis, 05-400 Otwock, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Błachnio
authors.affiliation: Mazovian Center for Lung Diseases and Tuberculosis, 05-400 Otwock, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jagodziński
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, 01-138 Warsaw, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Zwolska
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, 01-138 Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Augustynowicz-Kopeć
mesh_terms: D000107:Acetylation; D019943:Amino Acid Substitution; D000995:Antitubercular Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism*; D001682:Biological Availability; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009154:Mutation; D011044:Poland; D012150:Polymorphism, Restriction Fragment Length; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid