Polymorphisms of promoter and coding regions of the arylamine N-acetyltransferase 2 (NAT2) gene in the Indonesian population: proposal for a new nomenclature

Polymorphisms of arylamine N-acetyltransferase 2 (NAT2) are reportedly associated with the risk of drug toxicities and development of various diseases. The present study examined NAT2 polymorphisms in both promoter and coding regions in the Indonesian population using PCR direct sequencing. The promoter and coding regions of NAT2 displayed 23 polymorphisms/variations, including eight new ones. Seven haplotypes in the promoter region and six haplotypes in the coding region were inferred. The haplotypes in promoter and coding regions showed limited combinations, and 13 combined haplotypes were inferred. The most frequent haplotypes were U1 (38.9%), U2 (33.5%) in the promoter region and NAT2*4 (37.3%), NAT2*6A (36.8%) in the coding region. When converted to predicted phenotypes, the studied population comprised 65.4% rapid acetylators and 35.6% slow acetylators according to bimodal distribution. According to trimodal distribution, frequencies of predicted phenotypes were 13.6, 50.8 and 35.6% for rapid, intermediate and slow acetylators, respectively. Frequencies of NAT2 alleles for the Indonesian population resembled those of other Southeast Asian populations. We also propose a new NAT2 nomenclature composed of haplotypes in the promoter region and conventional NAT2 haplotypes in the coding region, symbolized by NAT2*4.U1, NAT2*4.U2, NAT2*4.U3, NAT2*4.U5, NAT2*4.U6, NAT2*4.U7, NAT2*6A.U1, NAT2*7B.U2, NAT2*7B.U3, NAT2*5B.U1, NAT2*5B.U4, NAT2*12A.U4 and NAT2*13.U1.