a genome-wide association study confirms vkorc1, cyp2c9, and cyp4f2 as principal genetic determinants of warfarin dose全基因组关联研究证实vkorc1、cyp2c9和cyp4f2华法林剂量的主要遗传因素.pdfVIP

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2017-09-05 发布于上海
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a genome-wide association study confirms vkorc1, cyp2c9, and cyp4f2 as principal genetic determinants of warfarin dose全基因组关联研究证实vkorc1、cyp2c9和cyp4f2华法林剂量的主要遗传因素.pdf

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a genome-wide association study confirms vkorc1, cyp2c9, and cyp4f2 as principal genetic determinants of warfarin dose全基因组关联研究证实vkorc1、cyp2c9和cyp4f2华法林剂量的主要遗传因素

A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose 1. 1. 1 1 2 Fumihiko Takeuchi , Ralph McGinnis *, Stephane Bourgeois , Chris Barnes , Niclas Eriksson , Nicole 1 1 1 1 1 Soranzo , Pamela Whittaker , Venkatesh Ranganath , Vasudev Kumanduri , William McLaren , Lennart 3 3 3 4 1 Holm , Jonatan Lindh , Anders Rane , Mia Wadelius , Panos Deloukas * 1 Wellcome Trust Sanger Institute, Hinxton, United Kingdom, 2 Uppsala Clinical Research Centre, Uppsala, Sweden, 3 Department of Clinical Pharmacology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden, 4 Department of Medical Sciences, Clinical Pharmacology, Uppsala University Hospital, Uppsala, Sweden Abstract We report the first genome-wide association study (GWAS) whose sample size (1,053 Swedish subjects) is sufficiently powered to detect genome-wide significance (p ,1.561027) for polymorphisms that modestly alter therapeutic warfarin dose. The anticoagulant drug warfarin is widely prescribed for reducing the risk of stroke, thrombosis, pulmonary embolism, and coronary malfunction. However, Caucasians vary widely (20-fold) in the dose needed for therapeutic anticoagulation, and hence prescribed doses may be too low (risking serious illness) or too high (risking severe bleeding). Prior work established that ,30% of the dose variance is explained by single nucleotide polymorphisms (SNPs) in the warfarin drug target VKORC1 and a