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Blood, 23 April 2009, Vol. 113, No. 17, pp. 3925-3930. Prepublished online as a Blood First Edition Paper on December 12, 2008; DOI 10.1182/blood-2008-09-176859. This Article Full Text (PDF) All Versions of this Article: blood-2008-09-176859v1 113/17/3925    most recent Alert me when this article is cited Alert me if a correction is posted 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 Li, C. Articles by Kurnik, D. Search for Related Content PubMed PubMed Citation Articles by Li, C. Articles by Kurnik, D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 2, 2008 Accepted November 29, 2008 Relative contribution of CYP2C9 and VKORC1 genotypes and early INR response to the prediction of warfarin sensitivity during initiation of therapy Chun Li, Ute I. Schwarz, Marylyn D. Ritchie, Dan M. Roden, C. Michael Stein, and Daniel Kurnik* Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, United States Departments of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, United States Center for Human Genetics, Vanderbilt University School of Medicine, Nashville, TN, United States Department of Medicine A and Division of Clinical Pharmacology and Toxicology, Sheba Medical Center, Tel Hashomer, Israel * Corresponding author; email: daniel.kurnik{at}sheba.health.gov.il. Genetic variants in CYP2C9 and VKORC1 strongly affect steady-state warfarin dose. However, these variants also affect early INR values during warfarin initiation. We examined whether CYP2C9/VKORC1 genotypes provide information about warfarin sensitivity additional to that provided by early INR responses. In 214 patients starting warfarin with INR-guided dose adjustments, we determined whether CYP2C9 and VKORC1 genotypes were associated with early measures of warfarin sensitivity (time to INRlower limit of therapeutic range; time to INR>4; and first stable warfarin dose) after adjusting for early (day 4-6) and week 1 (day 7-9) INR values. Early INRs were associated with all outcomes (all P<0.001) and were more informative than genotypes. For time-to-INRlower-limit-of-therapeutic-range, adding either early INRs or genotypes to a baseline model (clinical variables only) increased the goodness-of-fit (R2) from 0.05 to 0.42 and 0.19, respectively (full model, R2=0.46). For first-stable-warfarin-dose, adding either early INRs or genotypes to the baseline model increased the R2 from 0.08 to 0.32 and 0.27, respectively (full model, R2=0.40). After inclusion of week 1 INRs, CYP2C9 (P=0.08) and VKORC1 (P=0.30) were not associated with stable warfarin dose. Thus, much of the information provided by CYP2C9 and VKORC1 genotypes during warfarin initiation is captured by the early INR response. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Relative contribution of VKORC1, CYP2C9, and INR response to warfarin stable dose Guilherme Suarez-Kurtz, Jamila A. Perini, Edimilson Silva-Assunção, and Claudio J. Struchiner Blood 2009 113: 4125-4126. [Full Text] [PDF] This article has been cited by other articles: V. Perez-Andreu, V. Roldan, A. I. Anton, N. Garcia-Barbera, J. Corral, V. Vicente, and R. Gonzalez-Conejero Pharmacogenetic relevance of CYP4F2 V433M polymorphism on acenocoumarol therapy Blood, May 14, 2009; 113(20): 4977 - 4979. [Abstract] [Full Text] [PDF]

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