VKORC1基因分型对华法林初始抗凝治疗的影响和临床指导意义

Effect of VKORC1 Genotyping on Warfarin Initial Anticoagulation Therapy and Clinical Guiding Significance

目的:探索中国人群VKORC1-1639G>A基因多态性对华法林初始剂量和INR值的影响。方法:纳入2019年1月~6月在阜外医院行人工瓣膜置换术后服用华法林、并进行基因检测的患者,采用匹配病例对照研究的方法,至少携带一个VKORC1-1639G等位基因的患者为突变型组,匹配相同例数的VKORC1-1639AA型患者作为野生型组,评估VKORC1-1639G>A基因型对初始华法林响应和剂量的影响。两组患者均在华法林治疗前采用PCR-RFLP的方法检测VKORC1和CYP2C9的基因型,首次给予3 mg的剂量后每日根据INR值调整剂量。结果:共纳入患者60人,两组各30人。两组患者人口统计学和临床基线信息无显著性差异;突变型组前2天、前3天、前4天华法林总剂量显著高于野生型组(除前2天两组总剂量差异P<0.05外,其余P<0.01);突变型组第2天、第3天、第4天、第5天INR值显著低于野生型组(P<0.01)。结论:与VKORC1-1639AA型患者相比,携带至少1个VKORC1-1639G等位基因的患者,前5天服用较大剂量华法林,INR值仍持续较低。

Objective:This study explored the association between the VKORC1(1639G>A)polymorphisms and the initial dose of warfarin and INR response in Chinese,in order to assist clinicians in decision-making based on INR response and VKORC1 genetic test results and to identify questions for further researches.Methods:In a matched case-control study,patients with at least one VKORC1-1639G allele who had initiated warfarin therapy following elective prosthetic heart valve replacement in Fuwai Hospital from January 2016 to May 2017 were included in the high-dose group.At the same time,well-matched patients with VKORC1-1639AA genotype were included in the low-dose group.We evaluated the effects of VKORC1-1639G>A on warfarin response and dose difference during initial anticoagulation therapy.Genotyping for VKORC1 and CYP2C9 was performed by PCR-RFLP prior to warfarin therapy.Results:A total of sixty patients were recruited in our study,including thirty patients in the high-dose group while thirty patients in the low-dose group.No significant difference was detected in demographic and baseline clinical data between the two groups.In the first 2,3 and 4 days,the total dosage of warfarin was significantly higher in the high-dose group than the low-dose group(P<0.01 or 0.05).On the second,third,fourth and fifth days,INRs were significantly lower in the high-dose group than the low-dose group(P<0.01).Conclusion:Patients with at least one VKORC1-1639G allele who have taken higher dose of warfarin still have lower INR values during the first few days.Therefore,according to the initial INR value,genetic testing decisions can be made selectively to shorten the time for patients with VKORC1-1639G allele to reach the target INR,thus achieving a better economic benefit ratio.