CYP2C9及APOE基因多态性与华法林稳态剂量和模型预测剂量的相关性研究  

Correlation between CYP2C9, APOE gene polymorphisms and stable warfarin and model prediction dose

作　　者：程弦 白树堂[1] CHENG Xian;BAI Shutang(The Second Department of Cardiothoracic Surgery, Haikou Hospital, Central South University Xiangya School of Medicine, Haikou, 570208, P.R.China)

机构地区：[1]中南大学湘雅医学院附属海口医院心胸外二科

出　　处：《中国胸心血管外科临床杂志》2019年第6期543-547,共5页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

基　　金：海南省国际科技合作专项项目(KJHZ2014-06)

摘　　要：目的研究中国海南地区人群细胞色素P450(cytochrome P450,CYP450)2C9(CYP2C9)和载脂蛋白(apolipoprotein E,APOE)基因多态性对华法林稳态剂量的影响,以及与模型预测剂量的相关性。方法选取2016年8月至2018年7月于我院心胸外二科就诊,并同意服用华法林抗凝需要行心脏瓣膜置换术的海南地区患者368例,其中男152例,年龄48.5~70.5(60.03±10.18)岁,女216例,年龄43.5~65.6(54.24±11.35)岁;通过聚合酶链式反应扩增CYP2C9和APOE基因片段,并对患者进行基因组单核苷酸多态性(single nucleotide polymorphisms,SNP)位点进行测序;同时记录患者的年龄、性别、体重、有无吸烟史和饮酒史,以及华法林稳态剂量等资料,并对这些临床资料进行回归分析,构建剂量预测模型。结果在368例患者中,CYP2C9基因型检测结果发现*1*1基因型患者301例,占比81.8%,*1*3型患者67例,占比18.2%,不同CYP2C9基因型患者,华法林稳态剂量差异有统计学意义(P<0.05);APOE基因型检测结果显示E2基因型患者93例,占比25.3%,E3基因型患者221例,占比60.1%,E4基因型患者54例,占比14.7%,不同APOE基因型患者华法林稳态剂量差异有统计学意义(P<0.05)。多元回归分析发现,患者的年龄、体重以及CYP2C9与APOE基因型均与患者的华法林稳态剂量有关,回归分析的相关系数R2=0.572,预测模型有统计学意义(P<0.05)。结论在我国海南地区人群中,存在CYP2C9以及APOE基因多态性,而且不同基因型的患者华法林稳态剂量存在显著差异;通过CYP2C9、APOE基因以及患者年龄、体重构建华法林稳态剂量预测模型,可以一定程度上解释不同患者之间华法林用药的差异。Objective To investigate the effect of CYP2C9 and APOE on the dose of stable warfarin and model prediction in Hainan population. Methods From August 2016 to July 2018, 368 patients who required heart valve replacement and agreed to take warfarin anticoagulation at the second department of cardiothoracic surgery in our hospital were enrolled, including 152 males aged 48.5-70.5 (60.03±10.18) years and 216 females aged 43.5-65.6 (54.24±11.35) years. CYP2C9 and APOE were amplified by polymerase chain reaction. The gene fragment was sequenced by the Single Nucleotide Polymorphisms (SNP) site. The patients' age, sex, weight, history of smoking and drinking, and the dose of stable warfarin were recorded. Regression analysis of these clinical data was made to construct a dose prediction model. Results Among 368 patients, CYP2C9 genotype test results showed 301 patients (81.8%) with *1 *1 genotype, and 67 patients (18.2%) with *1 *3 type. For different CYP2C9 genotype patients, the difference was statistically significant in the dose of stable warfarin (P<0.05). The results of APOE genotype showed 93 patients (25.3%) with E2 genotype, 221 patients (60.1%) with E3 genotype, and 54 patients (14.7%) with E4 genotype;the dose of stable warfarin in patients with different APOE genotypes was statistically significant (P<0.05). Multiple regression analysis showed that patients' age, body weight, and CYP2C9 and APOE genotypes were correlated with the dose of stable warfarin. The correlation coefficient R2 was 0.572, and the prediction model was statistically significant (P<0.05). Conclusion CYP2C9 and APOE gene polymorphisms exist in Hainan population. There is significant difference in the dose of stable warfarin among different genotypes of patients. The model to predict stable warfarin can partly explain the difference of warfarin among different patients.

关 键 词：华法林剂量 细胞色素P4502C9 载脂蛋白E 模型预测 

分 类 号：R654.2[医药卫生—外科学]