Comparison of genetic polymorphisms of theNAT2gene between Korean and four other ethnic groups

Abstract

N-acetyltransferase 2 (NAT2) is responsible for the acetylation of numerous drugs and in the transformation of aromatic and heterocyclinc amines into carcinogenic intermediates. Polymorphism of NAT2 may contribute to interindividual variability in such acetylation. The aim of this study was to determine the allele frequencies of polymorphisms of the NAT2 gene, analyse linkage disequilibrium (LD) block and haplotypes in Koreans and compare them with those of other ethnic groups. We analysed genetic polymorphisms in all functional promoter and exons of the NAT2 gene by direct sequencing of genomic DNA from 192 healthy Korean subjects. The LD and haplotype blocks of these subjects were constructed from genotype data using an expectation-maximization algorithm. We compared these allele frequencies, LD block and haplotype structure with those of other ethnic groups registered on the International HapMap database. We identified 33 polymorphisms including six novel single nucleotide polymorphisms, -10778T>C, -10777A>G, -10351A>G, -10199C>T and -10104G>T in promoter and 578C>T in exon2 (T193M) in the Korean subjects tested. All allele frequencies reported in the Koreans were similar to those of Asians except for one allele (rs4345600, -9306A>G), whereas African and European groups had different frequencies in exon2. The haplotype structure and LD block among the five groups also revealed significant differences. Ethnic differences in the NAT2 genotype frequencies may be one of the important factors explaining variability in cancer incidence and drug toxicity. Our observations could be useful in assessing the susceptibility of different populations to cancer and contribute to better predictions of the pharmacokinetics and pharmacodynamics of drugs that are metabolized by NAT2, in different populations.