Article Text

PDF

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.

    Statistics from Altmetric.com

    Request permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.