title: Warfarin Dose Model for the Prediction of Stable Maintenance Dose in Indian Patients.
abstract: The main aim of this study was to screen various genetic and nongenetic factors that are known to alter warfarin response and to generate a model to predict stable warfarin maintenance dose for Indian patients. The study comprised of 300 warfarin-treated patients. Followed by extensive literature review, 10 single-nucleotide polymorphisms, that is, VKORC1-1639 G>A (rs9923231), CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), FVII R353Q (rs6046), GGCX 12970 C>G (rs11676382), CALU c.*4A>G (rs1043550), EPHX1 c.337T>C (rs1051740), GGCX: c.214+597G>A (rs12714145), GGCX: 8016G>A (rs699664), and CYP4F2 V433M (rs2108622), and 5 nongenetic factors, that is, age, gender, smoking, alcoholism, and diet, were selected to find their association with warfarin response. The univariate analysis was carried out for 15 variables (10 genetic and 5 nongenetic). Five variables, that is, VKORC1-1639 G>A, CYP2C9*2, CYP2C9*3, age, and diet, were found to be significantly associated with warfarin response in univariate analysis. These 5 variables were entered in stepwise and multiple regression analysis to generate a prediction model for stable warfarin maintenance dose. The generated model scored R2of .67, which indicates that this model can explain 67% of warfarin dose variability. The generated model will help in prescribing more accurate warfarin maintenance dosing in Indian patients and will also help in minimizing warfarin-induced adverse drug reactions and a better quality of life in these patients.
authors.affiliation: 1 National Institute of Immunohaematology (ICMR), Department of Thrombosis and Haemostasis, KEM Hospital, Parel, Mumbai, India.
authors.forename: Tejasvita
authors.initials: T
authors.lastname: Gaikwad
authors.affiliation: 2 Surat Raktadan Kendra & Research Centre, Regional Blood Transfusion Centre, Surat, Gujarat, India.
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.affiliation: 3 School of Mathematics and Statistics, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Avery
authors.affiliation: 4 Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Farhad
authors.initials: F
authors.lastname: Kamali
authors.affiliation: 1 National Institute of Immunohaematology (ICMR), Department of Thrombosis and Haemostasis, KEM Hospital, Parel, Mumbai, India.
authors.forename: Shrimati
authors.initials: S
authors.lastname: Shetty
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D054796:Drug Dosage Calculations; D056726:Genetic Association Studies; D006801:Humans; D007194:India; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012307:Risk Factors; D014859:Warfarin / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D014859:Warfarin
keywords: India; dosing algorithm; multiple regression analysis; warfarin