title: Effect of gene polymorphims on the warfarin treatment at initial stage.
abstract: The adverse reactions of warfarin that were found mainly occurred in the first month. This study was carried out to observe the effect of gene polymorphisms on the warfarin therapy at the initial stage. Four-hundred and sixty Chinese patients began warfarin treatment with daily 2.5 mg after heart valve replacement operations were enrolled. The daily international normalized ratio (INR) for anticoagulation were recorded till the seventh day. Blood samples were collected and used to detect genotypes for VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650. INR and their changes were compared among genotypes. INR was partially correlated with the VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650 polymorphisms from the third, fourth and sixth day on, respectively. VKORC1 rs7294 and CYP4F2 rs2108622 carriers responded lower than the wild genotype, whereas CYP2C9 rs1057910 and ORM1 rs17650 carriers responded higher, respectively. Fifty percent of AA/*1*3/CC/*S*S patients and 16% of AA/*1*1/CC/*S*S patients were over anticoagulation treated with INR >4.0 at the third day. Ninety percent of VKORC1 rs7294 carrier patients have INR <1.63, a mark of the 25% of lower responders of the wild genotype. Our study provided another kind of evidence that VKORC1 rs7294, CYP2C9 rs1057910, CYP4F2 rs2108622 and ORM1 rs17650 affected the action of warfarin in different styles. Patients with AA/*1*1/CC/*S*S, AA/*1*3/CC/*S*S should use a less initial dosage to avoid over anticoagulation, and patients with VKORC1 rs7294 should use larger initial dose to proof an effective therapy.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Changsha, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiothoracic Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: H H
authors.initials: HH
authors.lastname: Jiang
authors.affiliation: Department of Cardiothoracic Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: D K
authors.initials: DK
authors.lastname: Wu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Changsha, China.
authors.forename: Y X
authors.initials: YX
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory, Zhongshan Hospital Xiamen University Translational Medicine Research Center, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.
authors.forename: H M
authors.initials: HM
authors.lastname: Ye
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Changsha, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Changsha, China.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Luo
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Changsha, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Changsha, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Changsha, China.
authors.forename: Y C
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Changsha, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Changsha, China.
authors.forename: H H
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.|Institute of Clinical Pharmacology, Central South University, Changsha, China.
authors.forename: L S
authors.initials: LS
authors.lastname: Wang
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D002681:China; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D000072470:Cytochrome P450 Family 4 / Q000235:genetics; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects*; D006801:Humans; D019934:International Normalized Ratio; D008875:Middle Aged; D009961:Orosomucoid / Q000235:genetics; D010597:Pharmacogenetics; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D009961:Orosomucoid; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases