Correlation between phenotype and polymorphism of Chinese Han's gene encoding N-acetyltransferase 1 / 中国药理学通报

ABSTRACT

Aim To establish the method of detecting the Arylamine N-acetyltransferase-1(NAT1) genotype and its distribution of polymorphism,and analyze the correlation between the genotype and the phenotype in a Chinese Hans population.Methods The peripheral blood samples from 140 Han people were collected and analyzed for NAT1 genotypes by multiple PCR and PCR-RFLP method.The NAT1 enzyme kinetics in leukocytes in 32 persons with different genotypes from 140 Han people,were determinated for NAT1 phenotype by HPLC,the values of intrinsic clearance(Clint) and V_(max) and Michaelis constant(K_m) of NAT1 were calculated for evaluation of para-aminobenozic acid as a specific substrate.Results The NAT1 genotype of Chinese Hans population was distinguished accurately by multiple PCR and PCR-RFLP methods,and was not interfered by the interaction of several restriction endonucleases.The allelic frequencies of NAT1~*3,NAT1~*4,NAT1~*10 and NAT1~*11 from 140 Han people,were 0.082,0.496,0.40 and 0.022,respectively.The frequency of NAT1~*4 allele was significantly lower than that of Caucasian populations,but higher than that of Southeast Asia and African.Frequencies of NAT1~*3 and NAT1~*11 allele were comparable with those of many Asian populations,but the frequency of NAT1~*10 allele was higher than that of in Europe and America populations.Compared with the activity of wild genotype NAT1 ~*4/~*4,activities of the homozygote or heterozygote NAT1~*10 genotypes which include the NAT1 ~*4/~*10,the NAT1 ~*10/~*10 and the NAT1 ~*10/~*3 were higher significantly(P