宁夏回族人群CYP2D6*10基因多态性及功能分析  

Analysis on polymorphism function of CYP2D6*10 in Ningxia Hui

作　　者：李居怡[1] 王健[2] 高鹏[1] 杜娟[1] 李宗吉[1] 

机构地区：[1]宁夏医科大学基础医学院,银川750004 [2]宁夏自治区人民医院

出　　处：《江苏医药》2010年第6期640-642,共3页Jiangsu Medical Journal

基　　金：宁夏自然科学基金(NZ07109);宁夏卫生厅重点科研课题(W200707)

摘　　要：目的探讨基因突变对人CYP2D6蛋白结构与功能的影响。方法采用等位基因特异扩增(ASA-PCR)及DNA测序技术分析宁夏回族人群CYP2D6*10(C188T)基因多态性,以生物信息学方法对突变造成的肝药酶活性的下降做出合理的解释。结果蛋白质基本性质分析工具(ProtParam)分析显示,在溶液中CYP2D6*10突变型蛋白的不稳定指数高于野生型,都高于阈值40;二级结构预测软件(DNAStar/Protean)分析显示,突变型蛋白的二级结构在第33位多了一个转角(Gamier-RobsonTurn);功能位点预测程序(MotifScan)对蛋白功能位点进行预测,结果显示CYP2D6*10野生型蛋白有2个P450酶激活位点,而突变型没有;信号肽预测程序(SignalP)分析显示,神经网络模型(NN)C-score计算结果为突变型蛋白没有信号肽,而野生型有。结论基因突变可引起CYP2D6蛋白结构与功能的改变;应用生物信息学方法对CYP2D6基因突变致使的酶活性的下降做出一些可能的解释是可行的。Objective To investigate the effect of gene mutation on the structure and function of CYP2D6 protein in human.Methods CYP2D6＊10 gene polymorphism in Ningxia Hui was analyzed using PCR-ASA and DNA sequencing technologies.The descending activity of liver drug enzyme due to gene mutation was explained by bioinformatics.Results The analysis of ProtParam demonstrated that the mutant protein index of instability was higher than wild-type in the solution,which were all higher than the threshold value of 40.The analysis of DNAStar/Protean demonstrated that the mutant protein＇s secondary structure had a additional Gamier-Robson Turn at the 33rdMotif Scan demonstrated that the CYP2D6＊10 wild protein had 2 active sites of P450 enzyme,but the mutant did not.The result of neural network model（NN） C-score was that the mutant protein had no signal peptide,but the wild had.Conclusion The gene mutation may cause the changes of CYP2D6 protein structure and function.It is feasible to explain CYP2D6 mutation-induced the reduction in the activity of enzymes by bioinformatics.

关 键 词：CYP2D6＊10 生物信息学 回族 

分 类 号：R394[医药卫生—医学遗传学]