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• W2013156742 abstract "Warfarin therapy management is challenging due to the greater than 10-fold interindividual variability in the therapeutic dose [ 1 Hirsh J. Fuster V. Ansell J. Halperin J.L. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. Circulation. 2003; 107: 1692-1711 Crossref PubMed Scopus (468) Google Scholar , 2 Gage B.F. Pharmacogenetics-based coumarin therapy. Hematology Am Soc Hematol Educ Program. 2006; : 467-473 Crossref PubMed Scopus (64) Google Scholar , 3 Yin T. Miyata T. Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1—rationale and perspectives. Thromb Res. 2007; 120: 1-10 Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar , 4 Millican E. Jacobsen-Lenzini P.A. Milligan P.E. Grosso L. Eby C. Deych E. Grice G. Clohisy J.C. Barrack R.L. Burnett R.S. Voora D. Gatchel S. Tiemeier A. Gage B.F. Genetic-based dosing in orthopaedic patients beginning warfarin therapy. Blood. 2007; 110: 1511-1515 Crossref PubMed Scopus (164) Google Scholar ]. Haplotypes in the gene of vitamin K epoxide reductase complex (VKORC1), encoding vitamin K epoxide reductase which is a target enzyme of warfarin, have been linked to the effective maintenance dose of warfarin [ 5 Rieder M.J. Reiner A.P. Gage B.F. Nickerson D.A. Eby C.S. McLeod H.L. Blough D.K. Thummel K.E. Veenstra D.L. Rettie A.E. Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose. N Engl J Med. 2005; 352: 2285-2293 Crossref PubMed Scopus (1234) Google Scholar , 6 Geisen C. Watzka M. Sittinger K. Steffens M. Daugela L. Seifried E. Muller C.R. Wienker T.F. Oldenburg J. VKORC1 haplotypes and their impact on the inter-individual and inter-ethnical variability of oral anticoagulation. Thromb Haemost. 2005; 94: 773-779 PubMed Google Scholar , 7 Marsh S. King C.R. Porche-Sorbet R.M. Scott-Horton T.J. Eby C.S. Population variation in VKORC1 haplotype structure. J Thromb Haemost. 2006; 4: 473-474 Crossref PubMed Scopus (49) Google Scholar , 8 Osman A. Enstrom C. Arbring K. Soderkvist P. Lindahl T.L. Main haplotypes and mutational analysis of vitamin K epoxide reductase (VKORC1) in a Swedish population: a retrospective analysis of case records. J Thromb Haemost. 2006; 4: 1723-1729 Crossref PubMed Scopus (50) Google Scholar ]. Vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) is a paralogous gene of VKORC1 and shares about 50% amino acid identity with VKORC1 protein [ 9 Rost S. Fregin A. Ivaskevicius V. Conzelmann E. Hortnagel K. Pelz H.J. Lappegard K. Seifried E. Scharrer I. Tuddenham E.G. Muller C.R. Strom T.M. Oldenburg J. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004; 427: 537-541 Crossref PubMed Scopus (968) Google Scholar , 10 Li T. Chang C.Y. Jin D.Y. Lin P.J. Khvorova A. Stafford D.W. Identification of the gene for vitamin K epoxide reductase. Nature. 2004; 427: 541-544 Crossref PubMed Scopus (581) Google Scholar ]. The active sites of VKORC1 are predicted to reside at the thioredoxin-like Cys132-X-X-Cys135 center embedded in the transmembrane region, and the mutagenesis at one of Cys residues lost their activity [ 11 Wajih N. Sane D.C. Hutson S.M. Wallin R. Engineering of a recombinant vitamin K-dependent gamma-carboxylation system with enhanced gamma-carboxyglutamic acid forming capacity: evidence for a functional CXXC redox center in the system. J Biol Chem. 2005; 280: 10540-10547 Crossref PubMed Scopus (68) Google Scholar , 12 Rost S. Fregin A. Hunerberg M. Bevans C.G. Muller C.R. Oldenburg J. Site-directed mutagenesis of coumarin-type anticoagulant-sensitive VKORC1: evidence that highly conserved amino acids define structural requirements for enzymatic activity and inhibition by warfarin. Thromb Haemost. 2005; 94: 780-786 PubMed Google Scholar ]. A recent study suggested that the complex's protein disulfide isomerase subunit provides electrons for the reduction of the Cys132-X-X-Cys135 center in VKORC1 [ [13] Wajih N. Hutson S.M. Wallin R. Disulfide-dependent protein folding is linked to operation of the vitamin K cycle in the endoplasmic reticulum. A protein disulfide isomerase-VKORC1 redox enzyme complex appears to be responsible for vitamin K1 2,3-epoxide reduction. J Biol Chem. 2007; 282: 2626-2635 Crossref PubMed Scopus (111) Google Scholar ]. The Cys132-X-X-Cys135 center in VKORC1 is perfectly conserved in VKORC1L1[ 9 Rost S. Fregin A. Ivaskevicius V. Conzelmann E. Hortnagel K. Pelz H.J. Lappegard K. Seifried E. Scharrer I. Tuddenham E.G. Muller C.R. Strom T.M. Oldenburg J. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004; 427: 537-541 Crossref PubMed Scopus (968) Google Scholar , 10 Li T. Chang C.Y. Jin D.Y. Lin P.J. Khvorova A. Stafford D.W. Identification of the gene for vitamin K epoxide reductase. Nature. 2004; 427: 541-544 Crossref PubMed Scopus (581) Google Scholar ], suggesting the functional importance of the VKORC1L1 protein as a reductase for vitamin K recycling. However, the function of VKORC1L1 is totally unknown, including whether or not the VKORC1L1 genotypes are associated with the variability of the effective warfarin dose [ [14] Wadelius M. Chen L.Y. Eriksson N. Bumpstead S. Ghori J. Wadelius C. Bentley D. McGinnis R. Deloukas P. Association of warfarin dose with genes involved in its action and metabolism. Hum Genet. 2007; 121: 23-34 Crossref PubMed Scopus (328) Google Scholar ]." @default.
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• W2013156742 title "No association between vitamin K epoxide reductase complex subunit 1-like 1 (VKORC1L1) and the variability of warfarin dose requirement in a Japanese patient population" @default.
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