In this retrospective cohort study,we aimed to identify the influence of the CYP2C9*3 and CYP4F2 rs2108622 gene alleles on over-anticoagulation and bleeding complications associated with warfarin therapy.A total of 19...In this retrospective cohort study,we aimed to identify the influence of the CYP2C9*3 and CYP4F2 rs2108622 gene alleles on over-anticoagulation and bleeding complications associated with warfarin therapy.A total of 196 patients were included,including 80 males,the mean age was 50.8±10.7 years,and the average follow-up was 26.9±11.8 months.These patients underwent heart valve replacement surgery in the Cardiovascular Surgery of Fujian Provincial Hospital between January 2018 and August 2019,who took warfarin for at least 3 months and had target international normalized ratio(INR)between 1.8 and 2.5.Genotypes of CYP2C9*3 and CYP4F2 rs2108622 genes were tested by polymerase chain reaction(PCR)-gene sequencing technique.SPSS19.0 software was utilized to analyze the association between genotypes and warfarin-related over-anticoagulation and bleeding complications.Of the 434 patient-years,18 severe bleedings and 59 mild ones occurred in 31 patients.Patients with CYP2C9*1/*3 were associated with a higher over-anticoagulation risk compared with the*1/*1 carriers(hazard rate(HR)7.10;95%confidence interval(CI):2.54–19.79,P<0.001).The CYP4F2 rs2108622 mutant genotype did not cause significant increase in bleeding risk(HR 0.89;95%CI:0.43–1.82,P=0.74)or over-anticoagulation(HR 0.43;95%CI:0.16–1.13,P=0.09).Meanwhile,Kaplan-Meier survival curves showed that the time to over-anticoagulation in CYP2C9*1/*3 carriers was significantly shorter compared with the*1/*1 carriers(log-rank test,P<0.001),while that in CYP4F2 rs2108622 mutant genotype patients was longer compared with the wild-type patients(P=0.05).CYP2C9*3 and CYP4F2 rs2108622 might be major predictive factors of over-anticoagulation for warfarin therapy in Chinese patients.展开更多
基金Startup Fund for scientific research,Fujian Medical University (Grant No. 2017XQ010)Beijing Medical and Health Fou ndation (Grant No. B183023),China。
文摘In this retrospective cohort study,we aimed to identify the influence of the CYP2C9*3 and CYP4F2 rs2108622 gene alleles on over-anticoagulation and bleeding complications associated with warfarin therapy.A total of 196 patients were included,including 80 males,the mean age was 50.8±10.7 years,and the average follow-up was 26.9±11.8 months.These patients underwent heart valve replacement surgery in the Cardiovascular Surgery of Fujian Provincial Hospital between January 2018 and August 2019,who took warfarin for at least 3 months and had target international normalized ratio(INR)between 1.8 and 2.5.Genotypes of CYP2C9*3 and CYP4F2 rs2108622 genes were tested by polymerase chain reaction(PCR)-gene sequencing technique.SPSS19.0 software was utilized to analyze the association between genotypes and warfarin-related over-anticoagulation and bleeding complications.Of the 434 patient-years,18 severe bleedings and 59 mild ones occurred in 31 patients.Patients with CYP2C9*1/*3 were associated with a higher over-anticoagulation risk compared with the*1/*1 carriers(hazard rate(HR)7.10;95%confidence interval(CI):2.54–19.79,P<0.001).The CYP4F2 rs2108622 mutant genotype did not cause significant increase in bleeding risk(HR 0.89;95%CI:0.43–1.82,P=0.74)or over-anticoagulation(HR 0.43;95%CI:0.16–1.13,P=0.09).Meanwhile,Kaplan-Meier survival curves showed that the time to over-anticoagulation in CYP2C9*1/*3 carriers was significantly shorter compared with the*1/*1 carriers(log-rank test,P<0.001),while that in CYP4F2 rs2108622 mutant genotype patients was longer compared with the wild-type patients(P=0.05).CYP2C9*3 and CYP4F2 rs2108622 might be major predictive factors of over-anticoagulation for warfarin therapy in Chinese patients.
