摘要
目的：了解细胞色素P450(cytochromes P450,CYP)2C19,N-乙酰基转移酶2(arylamine N- acetyltransferase 2,NAT2)和硫嘌呤甲基转移酶(thiopurine S-methyltransferase,TPMT)基因常见的遗传多态性在河南地区汉族人群中的分布及其频率。方法：应用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)对210名河南地区汉族人群的CYP2C19突变基因(*2和*3)、NAT2突变基因(*6和*7)和TPMT突变基因(*3A,*3B和*3C)进行检测。用聚合酶链反应-等位基因特异性扩增(PCR-ASA)对NAT2突变基因(*5)和TPMT突变基因(*2)进行检测。结果：CYP2C19*2和*3等位基因分布频率分别为34．76%和6．4%,同时携带2个等位突变基因的慢基因型频率占14．8%。NAT2*4(wt),*5(341C),*6(590A)和*7(857A)等位基因分布频率分别为59．1%,4．1%,26．4%和9．5%,慢基因型分布频率占19．5%。TPMT*3C等位基因分布频率为1．2%,未发现TPMT*2,TPMT*3A或TPMT*3B。结论：CYP2C19,NAT2和TPMT基因常见的遗传多态性在汉族人群中的分布及其频率与白人存在明显差异,这将有助于我国汉族人群临床药动学研究和给药剂量的确定。
AIM： To determine the distribution and frequency of functionally important allelic variants in the cytochromes P450 （CYP） 2C19, arylamine N-acetyhransferase 2 （NAT2）, and thiopurine S-methyhransferase （TPMT） genes in the Han Chinese population and compare them with those of other ethnic populations. METHODS： Genotyping was carried out in a total of 210 unrelated Han Chinese volunteers derived from He-nan area. CYP2C19 variants （ ＊ 2 and ＊ 3）, NAT2 variants （ ＊ 6 and ＊ 7）, and TPMT variants （ ＊ 3A, ＊ 3B, and ＊ 3C） were detected using polymerase chain reaction/restriction fragment length polymorphism （PCR-RFLP） assays. Detection of NAT2 ＊ 5 and TPMT ＊ 2 were performed using allele-specific polymerase chain reaction assays. RESULTS： Allele frequencies of CYP2C19 ＊ 2 and ＊ 3 occurred with 34.76 % and 6.4 %, respectively. Thirty-one persons （ 14.8＂ % ） carried two of these CYP2C19 alleles responsible for poor metabolizing activity. The frequencies of specific NAT2 alleles were 59.1%, 4.1%, 26.4 %, and 9.5 % for ＊ 4 （wild-type）, ＊ 5 （341C）, ＊ 6 （590A）, and ＊ 7 （857A）, respectively. Genotyping of three different single nucleotide polymorphisms in the NA T2 gene revealed that the frequency of slow acetylators was 19.5 %. TPMT ＊ 3C had an allelic frequency of 1.2 %. TPMT＊ 2, TPMT＊ 3A, or TPMT＊ 3B was not detected in the analysed samples. CONCLUSION： The overview of allele distribution for drug-metabolizing enzymes CYP2C19, NAT2, and TPMT among a Han Chinese population shows obvious difference to Caucasians. The data will be useful for clinical pharmacokinetic investigation and drug dosage administration to Han Chinese population.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2006年第8期561-566,共6页
Chinese Journal of New Drugs and Clinical Remedies
基金
the Engineering Project for Innovative Scholars of He-nan Province(2004107014).This work was carried out in He-nan Key Laboratory for Molecular Medicine.
关键词
代谢
酶类
多态现象(遗传学)
药物代谢酶
汉族
metabolism
enzymes
polymorphism （genetics）
drug-metabolizing enzymes
Han Chinese
