CYP2C9基因多态性对P450酶含量和CYP2C9活性的影响  

Impact of CYP2C9 polymorphism on the content of P450 and CYP2C9 activity in human liver microsomes

作　　者：赵芸慧[1] 虞建刚[1] 马虹[1] 王俊科[1] 

机构地区：[1]中国医科大学附属第一医院,110001

出　　处：《山西医药杂志（上半月）》2010年第10期914-916,共3页Shanxi Medical Journal

基　　金：辽宁省教育厅课题(05L551)

摘　　要：目的检测CYP2C9基因多态性是否对人肝微粒体P450酶含量和CYP2C9酶活性产生影响。方法 203例行肝脏部分切除手术的汉族患者,静脉采血2mL用于DNA提取以及基因型测定。取病灶周围区域的正常肝组织提取肝微粒体。筛选出的不同基因型患者(CYP2C9野生型和突变体),选择不同基因型的样本进行微粒体P450酶含量测定,按照公式计算P450含量:P450(nmol/mg)=吸光度(A)(450-490nm)×1000(μm)/91(mmol/L)(摩尔消光系数)×蛋白终浓度(mg/mL),A(450-490nm)表示从波长490～450nm的吸光度值差。筛选出的不同基因型患者(CYP2C9野生型和突变体),比较肝微粒体内P450酶的含量和对CYP2C9活性探针甲苯磺丁脲的代谢速率的影响。结果 203例样本检出野生型196例,突变型杂合子7例,突变型纯合子未能检出。7例随机选择的野生型个体和7例突变型个体组平均P450酶含量分别为0.81、0.76nmol/mg,两组比较差异无统计学意义(P>0.05),7例野生型个体和7例突变型个体组甲苯磺丁脲的代谢速率分别为1.7和0.6nmol.min-1.mg-1蛋白,两组差异有统计学意义(P<0.01)。结论 CYP2C9基因多态性对肝微粒体中细胞色素P450酶含量没有显著影响。CYP2C9基因多态性降低肝微粒体中细胞色素CYP2C9酶活性。Objective To measure the impact of CYP2C9 polymorphism on the content of P450 and CYP2C9 activity in human liver microsomes. Methods Two hundred and three cases were chosen,who were picked up for hepatic partial excision under general anesthesia. Two-milliliter venous blood was taken after anesthesia for DNA extraction and genotyping. Genotyping was performed by multiplex polymerase chain reaction （PCR） and restriction enzyme digestion with Nsi Ⅰ. Two different groups were created according to genotype,wild-type and mutation-type. The content of P450 and activities of CYP2C9 were compared between the two groups.Results In the two hundred and three cases,one hundred and ninety-six cases belonged to wild type; seven cases belonged to mutation heterozygote and mutation homozygote was not detected. For the group of wild type,the content of P450 was 0.76 nmol/mg and for the other group,mutation group,was 0.81 nmol/mg （P0.05）. For the two groups （wild type group and mutation group）,the metabolic rate of tobutamide was 1.7 nmol·min-1·mg-1 protein and 0.6 nmol·min-1·mg-1 protein,respectively（P0.01）.Conclusion CYP2C9 polymorphism had no effect on the content of P450 in human liver microsome. CYP2C9 polymorphism decreased the activity of CYP2C9.

关 键 词：微粒体 肝 细胞色素 P450系统 多态性 单核苷酸 

分 类 号：R394[医药卫生—医学遗传学]