title: The Impact of Gene Polymorphisms on Anticoagulation Control With Warfarin.
abstract: Differences in warfarin maintenance dosages based on the presence of polymorphisms in VKORC1, CYP2C9, CYP4F2, and ORM1 can be determined through dosage adjustment according to routine guidelines. Little is known about whether routine therapy could provide consensus anticoagulation control for patients with different genotypes. This study was carried out to compare anticoagulant control in patients with different genotypes. Six hundred seventy patients using warfarin according to Chinese guidelines were enrolled. Warfarin dosages and monitored international normalized ratios (INRs) were recorded. Genotypes of VKORC1 rs9923231, CYP4F2 rs2108622, CYP2C9 rs1057910, and ORM1 rs17650 polymorphisms were determined. Warfarin dosages and INR were compared between genotypes. Patients with the AGCC*F*F*1*1 polymorphism took longer than patients with the AACC*F*F*1*1 polymorphism (20 vs 5 days, P < .001) to achieve the targeted INR range. The INR values of patients with AACC*F*F*1*3 were unstable and did not enter the stable state control phase until after 35 days. The peak INR of patients with the AACC*F*F*1*3 polymorphism was exceedingly high, with some values exceeding the control range limit of 3.0. Patients with the AACC*F*S*1*1 or AACT*F*F*1*1 polymorphisms exhibited similar INR values as the patients with the AACC*F*F*1*1 polymorphism. This study found that routine medication with warfarin provides significantly different levels of anticoagulant control between patients with wild-type genotypes and patients with heterozygous polymorphism genotypes of VKORC1 rs9923231 or CYP2C9 rs1057910. Patients with heterozygous polymorphism genotypes of VKORC1 or CYP2C9 require genotype-directed therapy with warfarin to increase efficacy and safety in anticoagulant treatment.
authors.affiliation: 1 Department of Cardiothoracic Surgery, Xiangya Hospital, Central South University, Chang Sha, Hu Na, China.
authors.forename: Hai He
authors.initials: HH
authors.lastname: Jiang
authors.affiliation: 2 Translational Medicine Center, Zhengzhou Central Hospital, Zhengzhou University, Zhengzhou, Henan Sheng, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: 3 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Chang Sha, Hu Na, China.|4 Institute of Clinical Pharmacology, Central South University, Chang Sha, Hu Na, China.
authors.forename: Yi Chen
authors.initials: YC
authors.lastname: Wang
authors.affiliation: 5 Department of Clinical Laboratory, Zhongshan Hospital, Xiamen University Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen University, Fujian, China.
authors.forename: Hui Ming
authors.initials: HM
authors.lastname: Ye
authors.affiliation: 3 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Chang Sha, Hu Na, China.|4 Institute of Clinical Pharmacology, Central South University, Chang Sha, Hu Na, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: 3 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Chang Sha, Hu Na, China.|4 Institute of Clinical Pharmacology, Central South University, Chang Sha, Hu Na, China.
authors.forename: Ya Xing
authors.initials: YX
authors.lastname: Zhou
authors.affiliation: 3 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Chang Sha, Hu Na, China.|4 Institute of Clinical Pharmacology, Central South University, Chang Sha, Hu Na, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 3 Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Chang Sha, Hu Na, China.|4 Institute of Clinical Pharmacology, Central South University, Chang Sha, Hu Na, China.
authors.forename: Lian Sheng
authors.initials: LS
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D014859:Warfarin / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: CYP2C9; CYP4F2; ORM1; VKORC1; warfarin