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

AUTOR(ES)

Smith, C A

RESUMO

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.

Documentos Relacionados

• Nucleotide sequence of rabbit NAT2 encoding polymorphic liver arylamine N-acetyltransferase (NAT).
• Nucleotide sequence of a full-length cDNA for arylamine N-acetyltransferase from rabbit liver.
• Cloning and Characterization of Arylamine N-Acetyltransferase Genes from Mycobacterium smegmatis and Mycobacterium tuberculosis: Increased Expression Results in Isoniazid Resistance
• Nucleotide sequence of an intronless gene for a human arylamine N-acetyltransferase related to polymorphic drug acetylation.
• Contribution of the N‐acetyltransferase 2 polymorphism NAT2*6A to age‐related hearing impairment