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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2477-2480. Prepublished online as a Blood First Edition Paper on November 16, 2006; DOI 10.1182/blood-2006-08-038984. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-08-038984v1 109/6/2477    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Loebstein, R. Articles by Gak, E. Search for Related Content PubMed PubMed Citation Articles by Loebstein, R. Articles by Gak, E. Related Collections Hemostasis, Thrombosis, and Vascular Biology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report A coding VKORC1 Asp36Tyr polymorphism predisposes to warfarin resistance Ronen Loebstein1, Ilana Dvoskin2, Hillel Halkin1, Manuela Vecsler2, Aharon Lubetsky1, Gideon Rechavi3, Ninette Amariglio3, Yoram Cohen3,4, Gie Ken-Dror5, Shlomo Almog1, and Eva Gak2 1 Institute of Clinical Pharmacology and Toxicology, 2 Institute of Human Genetics, 3 Cancer Research Center, and 4 Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Israel; 5 Department of Epidemiology and Preventive Medicine, Sackler School of Medicine, Tel Aviv University, Israel CYP2C9 and VKORC1 genetic variants are associated with low and intermediate warfarin dose requirements, but markers of high doses are less well characterized. We analyzed the VKORC1 coding sequence and known CYP2C9 and VKORC1 polymorphisms in 15 selected warfarin-resistant (dose, 80 to 185 mg/wk) and 8 warfarin-sensitive patients (7 to 13 mg/wk) and 99 unselected controls (8 to 105 mg/wk). We identified a coding VKORC1 Asp36Tyr polymorphism in 7 of 15 resistant compared with 0 of 8 sensitive patients (P = .026) Carriers of Asp36Tyr in the control group (8 of 99) required significantly higher warfarin doses of 80.9 ± 10.1 mg/wk compared with 42.7 ± 7.5 mg/wk in noncarriers (F = 9.79, P = .002). Asp36Tyr was significantly associated with doses of more than 70 mg/wk (odds ratio, 13.0; 95% confidence limit, 1.3 to 124.2), while doses of 20 to 70 mg/wk were associated with Asp36Tyr (partial r2 = .11; P = .004), CYP2C9*2 and *3 (r2 = .08; P = .01), and VKORC1*2 and *3 markers (r2 = .05; P = .05). All Asp36Tyr carriers also had VKORC1*1 tag–single nucleotide polymorphisms (tag-SNPs) indicating a new haplotype. Asp36Tyr was common in Jewish ethnic groups of Ethiopian (15%) and Ashkenazi (4%) origin. We suggest that Asp36Tyr is a new marker of the high end of the warfarin dosing range. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Aklillu, C. Leong, R. Loebstein, H. Halkin, and E. Gak VKORC1 Asp36Tyr warfarin resistance marker is common in Ethiopian individuals Blood, April 1, 2008; 111(7): 3903 - 3904. [Full Text] [PDF]

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