染料木素临床不良反应与CYP1A2、UGT1A7基因多态性研究

Study on genistein clinical adverse reaction and gene polymorphism of CYP1A2、UGT1A7

目的:探讨染料木素临床不良反应与CYP1A2、UGT1A7基因多态性的相关性。方法:114例健康志愿者随机分为试验组与对照组,试验组分别口服染料木素一个剂量50、100、200mg,每人服药1次,观察3d了解有无不良反应发生;用限制性片段长度多态性聚合酶链反应(RFLR-PCR)扩增基因片段并酶切电泳观察分析CYP1A2G2964A、C734A和UGT1A7Trp208Arg的多态性。结果:试验组及对照组的基因型及等位基因分布差异无统计学意义(P>0.05)。试验组受试者根据有无不良反应的出现分为两组基因,CYP1A2G2964A基因:不良反应组14例受试者中有10例的基因型为G/A(占71.43%),而无不良反应组41例受试者中有22例的基因型为G/G(占53.66%);CYP1A2C734A基因:不良反应组13例受试者中有7例的基因型为C/A(占53.85%),而无不良反应组32例受试者中有16例的基因型为A/A(占50.00%);UGT1A7Trp208Arg基因:不良反应组15例受试者中有12例的基因型为Trp/Trp(占80.00%),并且无不良反应组53例受试者中有32例的基因型也为Trp/Trp(占60.38%)。结论:染料木素不良反应组中CYP1A2G2964A基因以G/A型较高,CYP1A2C734A基因以G/G型较高;UGT1A7基因以Trp/Trp型较高。

AIM： In order to discuss the relation between clinical adverse reaction and gene polymorphism of CYP1A2, UGT1A7 when using genistein. METHODS ： 114 cases of healthy volunteers were randondy divided into 2 groups： model group, and normal group, the model group take genistein 50, 100, 200 mg by oral, and each dose of genistein was observed 3 days for the occurrence of adverse re.action. Gene fragment was amplified by restriction fragment length polymorphism polymerase chain reaction（RFLR-PCR）, and polymorphism of CYP1A2G2964A, C734A and UGT1A7Trp208Argwas analysised by enzyme electrophoresis. RESULTS： There had no significant difference of gene distribution between model and normal groups（ P 〉 0.05）. Model group was divided into 2 groups of genotypes according to adverse reaction occurrence, CYP1A2G2964A gene： the 10 cases genotype among 14 cases in adverse reaction group was G/A（account 71.43% ）, but 22 cases genotype among 41 cases in no adverse reaction was G/G （account 53.66% ）; CYPIA2C734A gene： 7 cases genotype among 13 cases in adverse reaction was C/A （ account 53.85 % ）, but 16 cases genotype among 32 cases in no adverse reaction was A/A（account 50.00% ）. UGT1A7Trp 208Arg Gene： 12 cases genotype among 15 cases in adverse reaction was Trp/Trp（account 80.00%）, and 32 cases genotype among 53 cases in no adverse reaction was Trp/Trp （ account 60.38%）. CONCLUSION： The relation gene in adverse reaction by using genistein is CYP1A2G2964A, CYP1A2C734A and UGT1A7, especially higher in G/A, C/A and Trp/Trp for each gene.