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Integration of gene...
Integration of genetic, clinical, and INR data to refine warfarin dosing
- Article/chapterEnglish2010
Publisher, publication year, extent ...
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2010-04-07
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Springer Science and Business Media LLC,2010
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-124510
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-124510URI
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https://doi.org/10.1038/clpt.2010.13DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:120333366URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Well-characterized genes that affect warfarin metabolism (cytochrome P450 (CYP) 2C9) and sensitivity (vitamin K epoxide reductase complex 1 (VKORC1)) explain one-third of the variability in therapeutic dose before the international normalized ratio (INR) is measured. To determine genotypic relevance after INR becomes available, we derived clinical and pharmacogenetic refinement algorithms on the basis of INR values (on day 4 or 5 of therapy), clinical factors, and genotype. After adjusting for INR, CYP2C9 and VKORC1 genotypes remained significant predictors (P < 0.001) of warfarin dose. The clinical algorithm had an R(2) of 48% (median absolute error (MAE): 7.0 mg/week) and the pharmacogenetic algorithm had an R(2) of 63% (MAE: 5.5 mg/week) in the derivation set (N = 969). In independent validation sets, the R(2) was 26-43% with the clinical algorithm and 42-58% when genotype was added (P = 0.002). After several days of therapy, a pharmacogenetic algorithm estimates the therapeutic warfarin dose more accurately than one using clinical factors and INR response alone.
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Wadelius, MiaUppsala universitet,Klinisk farmakogenomik och osteoporos(Swepub:uu)miawadel
(author)
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Kimmel, S.
(author)
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Anderson, J. L.
(author)
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Jorgensen, A. L.
(author)
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Pirmohamed, M.
(author)
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Caldwell, M. D.
(author)
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Limdi, N.
(author)
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Burmester, J. K.
(author)
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Dowd, M. B.
(author)
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Angchaisuksiri, P.
(author)
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Bass, A. R.Karolinska Institutet
(author)
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Chen, J.
(author)
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Eriksson, N.Uppsala universitet,Institutionen för medicinska vetenskaper,Uppsala kliniska forskningscentrum (UCR)
(author)
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Rane, A.
(author)
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Lindh, J. D.Karolinska Institutet
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Carlquist, J. F.
(author)
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Horne, B. D.
(author)
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Grice, G.
(author)
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Milligan, P. E.
(author)
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Eby, C.
(author)
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Shin, J.
(author)
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Kim, H.
(author)
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Kurnik, D.
(author)
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Stein, C. M.
(author)
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McMillin, G.
(author)
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Pendleton, R. C.
(author)
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Berg, R. L.
(author)
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Deloukas, P.
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Gage, B. F.
(author)
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Uppsala universitetKlinisk farmakogenomik och osteoporos
(creator_code:org_t)
Related titles
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In:Clinical Pharmacology and Therapeutics: Springer Science and Business Media LLC87:5, s. 572-5780009-92361532-6535
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To the university's database
- By the author/editor
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Lenzini, P.
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Wadelius, Mia
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Kimmel, S.
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Anderson, J. L.
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Jorgensen, A. L.
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Pirmohamed, M.
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show more...
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Caldwell, M. D.
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Limdi, N.
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Burmester, J. K.
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Dowd, M. B.
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Angchaisuksiri, ...
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Bass, A. R.
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Chen, J.
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Eriksson, N.
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Rane, A.
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Lindh, J. D.
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Carlquist, J. F.
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Horne, B. D.
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Grice, G.
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Milligan, P. E.
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Eby, C.
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Shin, J.
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Kim, H.
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Kurnik, D.
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Stein, C. M.
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McMillin, G.
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Pendleton, R. C.
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Berg, R. L.
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Deloukas, P.
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Gage, B. F.
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Clinical Pharmac ...
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Uppsala University
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Karolinska Institutet