Structural heterogeneity of Caucasian N-acetyltransferase at the NAT1 gene locus

Arch Biochem Biophys. 1993 Feb 15;301(1):71-6. doi: 10.1006/abbi.1993.1116.


The human N-acetylation polymorphism is a genetic trait phenotypically reflected by differences in N-acetyltransferase (NAT) activity with therapeutic agents (rapid and slow acetylation), but a genetic invariability in N-acetylation of some arylamine drugs is also known. There are two highly similar human NAT genes: NAT1 is thought to encode a genetically invariant protein, whereas NAT2 has conclusively been shown to represent a polymorphic locus. This study demonstrates the presence of discrete NAT1 structural variants among Caucasians. These were detected by direct sequencing of 1.6-kilobase NAT1 fragments generated by the polymerase chain reaction with liver and leukocyte DNA from 13 subjects of established acetylator phenotype and NAT2 genotype. A prominent alteration in one of the variants was obliteration of the consensus polyadenylation signal (AATAAA-->AAAAAA). Several mutations were discernible in all regions of the second variant allele, including silent (codon 153) and nonsilent (Ser-214-->Ala) substitutions in the coding region and deletion of nine bases from an AT-rich segment in the 3' untranslated region. One-half of the unrelated subjects were either homozygous or heterozygous for the mutant NAT1 alleles, both of which obeyed a Mendelian inheritance pattern. These novel results unambiguously show that human NAT1, like NAT2, is a polymorphic locus.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Arylamine N-Acetyltransferase / genetics*
  • Base Sequence
  • DNA / chemistry*
  • DNA / genetics
  • Genetic Variation*
  • Genotype
  • Heterozygote
  • Humans
  • Leukocytes / chemistry
  • Liver / chemistry
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Polymerase Chain Reaction
  • Whites / genetics*


  • DNA
  • Arylamine N-Acetyltransferase