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J Med Genet 34:758-760 doi:10.1136/jmg.34.9.758
  • Research Article

A simplified assay for the arylamine N-acetyltransferase 2 polymorphism validated by phenotyping with isoniazid.

  1. C A Smith,
  2. M Wadelius,
  3. A C Gough,
  4. D J Harrison,
  5. C R Wolf,
  6. A Rane
  1. ICRF Molecular Pharmacology Unit, Biomedical Research Centre, Ninewells Hospital, Dundee, UK.

      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.