POR相关基因多态性对华法林维持剂量的影响  

Impact of POR Polymorphisms on Warfarin Maintenance Dose

作　　者：郑绮姗[1] 赵立子[2] 刘锐锋[1] ZHENG Qishan;ZHAO Lizi;LIU Ruifeng(Department of Pharmacy,Zhongshan City People’s Hospital,Zhongshan 528403,China;School of Pharmaceutical Sciences,Sun Yat-Sen University,Guangzhou 510006,China)

机构地区：[1]中山市人民医院药学部,广东中山528403 [2]中山大学药学院,广东广州510006

出　　处：《生物化工》2023年第1期71-75,共5页Biological Chemical Engineering

基　　金：中山市医学科研项目(2016A020107)。

摘　　要：目的:探讨POR相关基因多态性对华法林维持剂量个体差异的影响。方法:2017年1月至2019年3月,在中山市人民医院、中山大学附属第一医院进行复查的188名机械瓣膜置换术患者被纳入研究,国际化标准比值及华法林维持剂量由患者的电子病历获得。POR A503V基因型检测采用直接测序法,POR 831-35C>T的基因型检测采用PCR-RFLP法。统计分析POR A503V、POR 831-35C>T各基因型对华法林剂维持剂量的影响。结果:POR A503V各基因型的平均华法林维持剂量分别为CC型(2.75±1.42)mg/d、CT型(2.78±1.41)mg/d、TT型(3.10±1.46)mg/d,组间差异无统计学意义;排除混杂因素后,组间差异仍无统计学意义。POR 831-35C>T各基因型的平均剂量为CC型(2.55±1.36)mg/d、CT型(2.90±1.40)mg/d、TT型(3.05±1.55)mg/d,CT型、TT型的剂量均显著高于CC型(P <0.05);排除混杂因素后,CT型、TT型组的剂量分别比CC型组高10.7%、16.0%(P<0.05)。结论:POR 831-35C>T突变后与华法林维持剂量升高相关,患者在制定华法林个体化用药方案时应参考POR 831-35C>T基因型。Objective:To study the impact of POR polymorphisms on the warfarin maintenance dose of Chinese patients with heart valve replacement.Methods:From January 2017 to March 2019,188 Chinese HVR patients reexamined in Zhongshan City People’s Hospital and The First Affiliated Hospital of Sun Yat-Sen University are recruited.International normalized ratio and warfarin maintenance doses are obtained from patients’electronic medical records.Polymorphism of POR A503V is detected by the direct sequencing and polymorphism of POR 831-35C>T is detected by polymerase chain reaction-restriction fragment length polymorphism.The impact on warfarin maintenance doses of each genotype group is analyzed.Results:The average maintenance dose of warfarin for POR A503V genotypes is(2.75±1.42)mg/d for CC genotype,(2.78±1.41)mg/d for CT genotype,and(3.10±1.46)mg/d for TT genotype;After excluding the confounding factors,there is no significant difference between the groups.The average dose of POR 831-35C>T genotype is(2.55±1.36)mg/d for CC genotype,(2.90±1.40)mg/d for CT genotype,and(3.05±1.55)mg/d for TT genotype.The dose of CT genotype and TT genotype is significantly higher than that of CC genotype(P<0.05);After excluding the confounding factors,the doses of CT type and TT type are 10.7%and 16.0%higher than those of CC type(P<0.05).Conclusion:POR 831-35C>T is another significant genetic factor contributed to the inter-individual variability of warfarin maintenance dose.

关 键 词：华法林 POR 单核苷酸多态性 维持剂量 个体差异 

分 类 号：R96[医药卫生—药理学]