中国胸心血管外科临床杂志

中国胸心血管外科临床杂志

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

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目的 研究中国海南地区人群细胞色素 P450(cytochromeP450,CYP450)2C9 和载脂蛋白(apolipoprotein E,APOE)基因多态性对华法林稳态剂量的影响,以及模型预测剂量的相关性。 方法 选取 2016 年 8 月至 2018 年 7 月于来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 292 例,占比 79.3%,*1*3 型患者 58 例占比 15.8%,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1APOE 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 为 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 steady-state dose of warfarin in Hainan. Methods From August 2016 to July 2018, 368 patients who required heart valve replacement and agreed to take Huafarin anticoagulatio at the department of cardiothoracic surgery in our hospital, 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 and sequenced by the Single Nucleotide Polymorphisms (SNP) site. The patients' age, sex, weight, history of smoking and drinking history, and warfarin stability were recorded. State dosage and other data; regression analysis of these clinical data to construct a dose prediction model. Results Among 368 patients, CYP2C9 genotype test results showed that 292 patients of *1*1 genotype accounted for 79.3%, and 58 patients of *1*3 type accounted for 15.8%. For different CYP2C9 genotype patients, the difference was statistically significant in warfarin steady-state dose (P<0.05). The results of APOE genotype showed 93 patients of E2 genotype, accounting for 25.3%, 221 patients of E3 genotype, accounting for 60.1%, and 54 patients of E4 genotype, accounting for 14.7%; the steady-state doses of warfarin in patients with different APOE genotypes were statistically significant (P<0.05). Multiple regression analysis showed that patients' age, body weight, and CYP2C9 and APOE genotypes were stable with warfarin. The correlation coefficient R2 was 0.572, and the predictive model was statistically significant (P<0.05). Conclusion CYP2C9 and APOE gene polymorphisms exist in Hainan population. There are significant differences in warfarin homeostasis dosage among different genotypes of patients. Warfarin steady-state dose prediction model can partly explain the difference of warfarin between different patients.

关键词: 华法林剂量; CYP2C9; APOE; 模型预测

Key words: Warfarin; CYP2C9; APOE; Model prediction

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