title: Effect of CYP2C9-VKORC1 interaction on warfarin stable dosage and its predictive algorithm.
abstract: This study aimed to identify the effect of CYP2C9-VKORC1 interaction on warfarin dosage requirement and its predictive algorithm by investigating four populations. Generalized linear model was used to evaluate the relationship between the interaction and warfarin stable dosage (WSD), whereas multiple linear regression analysis was applied to construct the WSD predictive algorithm. To evaluate the effect of CYP2C9-VKORC1 interaction on the predictive algorithms, we compared the algorithms with and without the interaction. The interaction was significantly associated with WSD in the Chinese and White cohorts (P values < 0.05). In the algorithms that considered the interaction, the predictive success rates improved by only 0.12% in the Chinese patients and by a maximum of 0.02% in the White patients under four different CYP2C9 classifications. Thus, VKORC1-CYP2C9 interaction can affect WSD. However, the discrepancy between the predictive results obtained using the predictive algorithm with and without CYP2C9-VKORC1 interaction was negligible and can therefore be disregarded.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Ji-Ye
authors.initials: JY
authors.lastname: Yin
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Mao
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Central South University, Changsha, 410078, Hunan, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Zhi-Yin
authors.initials: ZY
authors.lastname: Luo
authors.affiliation: Clinical Pharmacy and Pharmacology Research Institute, The Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
authors.forename: Sheng-Lan
authors.initials: SL
authors.lastname: Tan
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D001777:Blood Coagulation / Q000187:drug effects*; D016009:Chi-Square Distribution; D002648:Child; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics* / Q000378:metabolism; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010597:Pharmacogenetics; D010641:Phenotype; D012307:Risk Factors; D064417:Vitamin K Epoxide Reductases / Q000235:genetics* / Q000378:metabolism; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: algorithms; epistasis; racial difference; single nucleotide polymorphism; warfarin