title: A simplified assay for the arylamine N-acetyltransferase 2 polymorphism validated by phenotyping with isoniazid.
abstract: Human arylamine N-acetyltransferase (NAT) activity is determined by two distinct genes, NAT1 and NAT2, and the classical acetylation polymorphism in NAT2 has been associated with a variety of disorders, including lupus erythematosus and arylamine induced cancers. Over 50% of the white population exhibit a slow acetylator phenotype. The genetic basis of the defect has been identified and several DNA based assays are available for genotyping studies. We present here a simplified, rapid PCR based assay for the identification of the major slow acetylator genotypes and validate it using isoniazid as probe drug. This assay was 100% predictive of phenotype. The three genotypes (homozygous mutated, heterozygous, and homozygous rapid) corresponded to a trimodal distribution of Ac-INH/INH metabolic ratios (slow, intermediate, and rapid) without overlapping.
authors.affiliation: ICRF Molecular Pharmacology Unit, Biomedical Research Centre, Ninewells Hospital, Dundee, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Wadelius
authors.forename: A C
authors.initials: AC
authors.lastname: Gough
authors.forename: D J
authors.initials: DJ
authors.lastname: Harrison
authors.forename: C R
authors.initials: CR
authors.lastname: Wolf
authors.forename: A
authors.initials: A
authors.lastname: Rane
mesh_terms: D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods*; D011110:Polymorphism, Genetic; D012606:Scotland; D013548:Sweden
chemical_list: D001191:Arylamine N-Acetyltransferase; D007538:Isoniazid