中国汉族人群中N-乙酰基转移酶1表型与基因多态性的关系  

Correlation between phenotype and polymorphism of Chinese Han's gene encoding N-acetyltransferase 1

作　　者：徐张巍[1] 许建明[1] 梅俏[1] 徐新华[1] 

机构地区：[1]安徽医科大学第一附属医院消化科,安徽合肥230032

出　　处：《中国药理学通报》2006年第10期1223-1228,共6页Chinese Pharmacological Bulletin

基　　金：安徽省教育厅自然科学基金资助项目(No2003KG199)

摘　　要：目的探讨汉族人群中N-乙酰基转移酶1(NAT1)基因多态性的分布特点,以及基因型和表型之间的相关分析,以评价NAT1乙酰化代谢多态性对5氨-基水杨酸等药物疗效的影响。方法收集140例汉族健康人的外周血,应用PCR、限制性片段长度多态性分析(RFLP)及多重PCR技术,进行NAT1等位基因分型研究。同时从140例检测标本中选择32份不同NAT1基因型进行外周血白细胞中NAT1的活性检测,计算NAT1内部清除率(C lint)、酶催化反应最大速率(Vm ax)和米氏常数(Km),代谢产物测定采用HPLC方法。结果联合应用PCR-RFLP及多重PCR方法可避免多种限制性内切酶之间的相互干扰,可准确区分不同NAT1基因型。在140例检测标本中,NAT1*3,NAT1*4,NAT1*10和NAT1*11的发生频率分别是8.2%,49.6%,40%和2.2%。NAT1*4的发生率明显低于欧美人群,但高于东南亚和非洲人群;NAT1*10的发生率高于欧美人群,NAT1*3和NAT1*11的发生率较低,与大多数亚洲人群基本一致。32份不同NAT1基因型中,与野生型NAT1*4*/4相比,NAT1*4*/10、NAT1*10/*10以及NAT1*10/*3酶活性属于快代谢表型(P<0.05);NAT1*11*/11和NAT1*4/*11酶活性要明显低于NAT1*4*/10、NAT1*10*/10和NAT1*10*/3(P<0.05),与NAT1*4*/3、NAT1*3/*3以及NAT1*4*/4差异无统计学意义。结论汉族人群中的NAT1基因型分布与其他国家检测情况有所差异。140名汉族人外周血NAT1表型检测结果差异较大,依据酶学代谢动力学参数的不同,NAT1*10的杂合子与纯合子均属于快代谢型基因,NAT1*11及其他基因型则属于慢代谢型基因,在本次实验中未发现中间代谢型基因。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 HaM 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 HaM people, were determinated for NAT1 phenotype by HPLC, the values of intrinsic clearance （Clint） and Vmax and Michaelis constant （Km ） 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 endo- nucleases. The allelic frequencies of NAT1^ ＊ 3, NAT1^ ＊4, NAT1^ ＊ 10 and NAT1^ ＊ 11 from 140 HaM 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 〈 0.05）. Activities of the NAT1 ^ ＊11/^ ＊ 11 and NAT1 ^ ＊4/^ ＊11 were lower than those of the homozygote or heterozygote NAT1 ^ ＊ 10 genotypes （ P 〈 0. 05 ）, but no different with activities of wild genotype and the NAT1 ^ ＊ 4/^ ＊ 3 and NAT1 ^ ＊ 3/^ ＊3. Conclusion The distribution of the NAT1 genotype in a Chinese Hans population was different from

关 键 词：NAT1 基因多态性 基因型 表型 

分 类 号：R195.1[医药卫生—卫生统计学] R345.53[医药卫生—卫生事业管理]