title: [Detection of mutation in NAT II gene as a method of determination of izoniazyd (INH) acetylation type in human population].
abstract: BACKGROUND
  Isoniazid (INH) is a drug widely used in the treatment of tuberculosis. INH is metabolized to acetylisoniazid by N-acetyltransferase (NAT) in the liver. The rate of INH acetylation is genetically determined. NAT isozymes are encoded at 2 loci; one encodes NAT1, formerly known as the monomorphic form of the enzyme, while the other encodes the polymorphic NAT2, which is responsible for individual differences in the ability to acetylate certain compounds. The objective of the present study was to apply the genotyping of the fast and slow acetylators for personalized therapeutic dose.
  
  
  METHODS
  Plasma concentrations of INH were determined with biological method in the authors modification. This method warrants high accuracy and secured repeatable results. Genomic DNA was isolated from the blood samples. DNA extracted by Blood DNA Kit and amplified by PCR by Spurr [1] with two primers. PCR product was cut separately with 4 different restriction enzymes: Dde1, Kpn1, Tag1, and BamH1.
  
  
  RESULTS
  Four different NAT 2 alleles were detected in the study population. The presence of any 2 mutant alleles defines the slow-acetylator genotype, whereas rapid acetylators have 1 or 2 wild-type NAT2*4 alleles.
  
  
  CONCLUSIONS
  On the basis of our results we suggest the using of NAT 2 genotyping for discrimination of the fast and slow acetylators in monitoring of tuberculosis therapy.
authors.affiliation: Zakład Mikrobiologii Instytutu Gruzlicy i Chorób Płuc w Warszawie.
authors.forename: Ewa
authors.initials: E
authors.lastname: Augustynowicz-Kopeć
authors.forename: Anna
authors.initials: A
authors.lastname: Zabost
authors.forename: Monika
authors.initials: M
authors.lastname: Kozińska
authors.forename: Sylwia
authors.initials: S
authors.lastname: Brzezińska
authors.forename: Zofia
authors.initials: Z
authors.lastname: Zwolska
mesh_terms: D000107:Acetylation; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid