A SIMPLIFIED ASSAY FOR THE ARYLAMINE N-ACETYLTRANSFERASE-2 POLYMORPHISM VALIDATED BY PHENOTYPING WITH ISONIAZID

Human arylamine N-acetyltransferase (NAT) activity is determined by tw o distinct genes, NAT1 and NAT2, and the classical acetylation polymor phism in NAT2 has been associated with a variety of disorders, includi ng lupus erythematosus and arylamine induced cancers. Over 50% of the white population exhibit a slow acetylator phenotype. The genetic basi s of the defect has been identified and several DNA based assays are a vailable for genotyping studies. We present here a simplified, rapid P CR based assay for the identification of the major slow acetylator gen otypes and validate it using isoniazid as probe drug. This assay was 1 00% predictive of phenotype. The three genotypes (homozygous mutated, heterozygous, and homozygous rapid) corresponded to a trimodal distrib ution of Ac-INH/INH metabolic ratios (slow, intermediate, and rapid) w ithout overlapping.