Pharmacogenetics of the human arylamine N-acetyltransferases

This review briefly describes current understanding of one of the earliest discovered pharmacogenetic polymorphisms of drug biotransformation affectin g acetylation of certain homo- and heterocyclic aromatic amines and hydrazi nes. This so-called acetylation polymorphism arises from allelic variation in one of the two known human arylamine N-acetyltransferase genes, namely N AT2, which results in production of NAT2 proteins with variable enzyme acti vity or stability. The NAT1 gene locus encodes a structurally related enzym e, NAT1, with catalytic specificity for arylamine acceptor substrates disti nct from that exhibited by NAT2, NAT1 function is also genetically variable in human populations. Clinical and toxicological consequences of genetic v ariation in NAT1 and NAT2 activity are discussed. Copyright (C) 2000 S. Kar ger AG. Basel.