The structure and characteristics of a fourth allele of polymorphic N-acetyltransferase gene found in the Japanese population.

Polymorphic N-acetyltransferase (NAT2), which exists in the human liver and metabolizes a wide spectrum of arylamine, is encoded by one gene (NAT2). We have identified the mutations of a fourth NAT2 allele (allele 4) which we previously found in the Japanese population. Compared with allele 1, which expresses a high enzyme activity, allele 4 has 3 nucleotide differences. 2 are missense mutations at nucleotide position (nt) 341 and 803. The other is a silent mutation at the KpnI site. From the result of expression studies of chimeric gene constructs between allele 1 and allele 4 in Chinese hamster ovary cells, nt 341 missense mutation of the allele 4 which causes the Ile-114 to Thr change is responsible for the low enzyme activity of NAT2 protein.