Xiaotong Xia1,2, Nianxu Huang3, Boxia Li4, Yan Li5, Lang Zou6, Dongdong Yuan7, Banghua Huang8, Yufei Bei9, Yuxin Liu10, Jinglan Fu1,2, Tingting Wu1,2, Wenjun Chen1,2, Shaojun Jiang1,2, Meina Lv1,2, Jinhua Zhang11,12. 1. Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China. 2. College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China. 3. Department of Pharmacy, Wuhan Asian Heart Hospital, Wuhan, Hubei, China. 4. Department of Pharmacy, The First Hospital of Lanzhou University, Lanzhou, Gansu, China. 5. Department of Pharmacy, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, Shangdong, China. 6. Department of Pharmacy, Second Affiliated Hospital, Army Medical University, Chongqing, China. 7. Department of Pharmacy, Zhengzhou Seventh People's Hospital, Zhengzhou, Henan, China. 8. Department of Pharmacy, the First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China. 9. Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. 10. Department of Pharmacy, Huaihe Hospital of He-Nan University, Kaifeng, Henan, China. 11. Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China. pollyzhang2006@126.com. 12. College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China. pollyzhang2006@126.com.
Abstract
PURPOSE: The purpose of this paper is to study the correlation between demographic and clinical factors and warfarin dose of patients in Chinese Han population taking warfarin and study gene polymorphisms impact of related gene loci (CYP2C9*3, VKORC1-1639G > A) on warfarin doses, to establish a model to predict initial standard dose and maintenance dose based on CYP2C9*3, VKORC1-1639G > A genotype. METHODS: The study collects the data of patients in our hospital and other subcenters which incorporates 2160 patients to establish the initial dose model and 1698 patients for the stable dose model, and sequences 26 multigene sites in 451 patients. Based on the patient's dosage, clinical data, and demographic characteristics, the genetic and non-genetic effects on the initial dose and stable dose of warfarin are calculated by using statistical methods, and the prediction model of initial standard dose and maintenance dose can be established via multiple linear regression. RESULTS: The initial dose of warfarin (mg/day) was calculated as (1.346 + 0.350 × (VKORC1-1639G > A) - 0.273 × (CYP2C9*3) + 0.245 × (body surface area) - 0.003 × (age) - 0.036 × (amine-iodine) + 0.021 × (sex))2. This model incorporated seven factors and explained 55.3% of the individualization differences of the warfarin drug dose. The maintenance dose of warfarin (mg/day) was calculated as (1.336 + 0.299 × (VKORC1-1639G > A) + 0.480 × (body surface area) - 0.214 × (CYP2C9*3) - 0.074 × (amine-iodine) - 0.003 × (age) - 0.077 × (statins) - 0.002 × (height))2. This model incorporated six factors and explained 42.4% of the individualization differences in the warfarin drug dose. CONCLUSION: The genetic and non-genetic factors affecting warfarin dose in Chinese Han population were studied systematically in this study. The pharmacogenomic dose prediction model constructed in this study can predict anticoagulant efficacy of warfarin and has potential application value in clinical practice.
PURPOSE: The purpose of this paper is to study the correlation between demographic and clinical factors and warfarin dose of patients in Chinese Han population taking warfarin and study gene polymorphisms impact of related gene loci (CYP2C9*3, VKORC1-1639G > A) on warfarin doses, to establish a model to predict initial standard dose and maintenance dose based on CYP2C9*3, VKORC1-1639G > A genotype. METHODS: The study collects the data of patients in our hospital and other subcenters which incorporates 2160 patients to establish the initial dose model and 1698 patients for the stable dose model, and sequences 26 multigene sites in 451 patients. Based on the patient's dosage, clinical data, and demographic characteristics, the genetic and non-genetic effects on the initial dose and stable dose of warfarin are calculated by using statistical methods, and the prediction model of initial standard dose and maintenance dose can be established via multiple linear regression. RESULTS: The initial dose of warfarin (mg/day) was calculated as (1.346 + 0.350 × (VKORC1-1639G > A) - 0.273 × (CYP2C9*3) + 0.245 × (body surface area) - 0.003 × (age) - 0.036 × (amine-iodine) + 0.021 × (sex))2. This model incorporated seven factors and explained 55.3% of the individualization differences of the warfarin drug dose. The maintenance dose of warfarin (mg/day) was calculated as (1.336 + 0.299 × (VKORC1-1639G > A) + 0.480 × (body surface area) - 0.214 × (CYP2C9*3) - 0.074 × (amine-iodine) - 0.003 × (age) - 0.077 × (statins) - 0.002 × (height))2. This model incorporated six factors and explained 42.4% of the individualization differences in the warfarin drug dose. CONCLUSION: The genetic and non-genetic factors affecting warfarin dose in Chinese Han population were studied systematically in this study. The pharmacogenomic dose prediction model constructed in this study can predict anticoagulant efficacy of warfarin and has potential application value in clinical practice.
Authors: Clive Kearon; Elie A Akl; Joseph Ornelas; Allen Blaivas; David Jimenez; Henri Bounameaux; Menno Huisman; Christopher S King; Timothy A Morris; Namita Sood; Scott M Stevens; Janine R E Vintch; Philip Wells; Scott C Woller; Lisa Moores Journal: Chest Date: 2016-01-07 Impact factor: 9.410