Relative contribution of CYP2C9 and VKORC1 genotypes and early INR response to the prediction of warfarin sensitivity during initiation of therapy

Li, Chun; Schwarz, Ute I.; Ritchie, Marylyn D.; Roden, Dan M.; Stein, C. Michael; Kurnik, Daniel

doi:10.1182/blood-2008-09-176859

Cited by 78 publications

(67 citation statements)

References 36 publications

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“…6,7,9,10,12,13,[21][22][23] Many studies have assessed genetic variants influencing the VKA response in adults. [4][5][6][7][8][9][10][11][12][13][14][15] In contrast, only a few small studies have investigated the effect of the VKORC1 and/or CYP2C9 genotype on VKA dose requirements in children. [24][25][26][27][28] Moreover, no study evaluated the potential influence of pharmacogenetic variables on anticoagulation control.…”

Section: Introductionmentioning

confidence: 99%

“…In the last decade, an increasing number of genetic variations affecting VKA pharmacodynamics and/or pharmacokinetics were found to have a major impact on the VKA dose in adults. [4][5][6][7][8][9][10][11][12][13][14][15] These genetic variations are found in single nucleotide polymorphisms (SNPs) in VKORC1, CYP2C9, and CYP4F2. [4][5][6][7][8][9][10][11][12][13][14][15] VKAs exert their anticoagulant effect by inhibiting the enzyme vitamin K epoxide reductase (VKORC1), thereby preventing vitamin K recycling and vitamin K-dependent carboxylation of the coagulation factors II, VII, IX, and X.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement

Moreau

Bajolle

Siguret

et al. 2012

Blood

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement

Moreau

Bajolle

Siguret

et al. 2012

Blood

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“…Such patients require lower doses of warfarin and they are less likely carriers of VKORC1 rare mutations, all of which could contribute to more accurate dosing (27,28). Estimated initial doses and stable maintenance doses did not differ among the group of genotypes, indicating that our pharmacogenetically based warfarin-dosing algorithm could effectively predict the actual warfarin maintenance dose, providing clinicians with a reliable tool for managing successful anticoagulation (33)(34)(35).…”

Section: Discussionmentioning

confidence: 97%

Prevalence of genetic polymorphisms of CYP2C9 and VKORC1 — Implications for warfarin management and outcome in Croatian patients with acute stroke

Šupe

Božina

Matijević

et al. 2014

Journal of the Neurological Sciences

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“…Poly morphisms in genes CYP2C9 (encoding the main cytochrome P4590 enzyme) and VKORC1 (encoding the warfarin target vitamin K epoxide reductase) were associated with variability in warfarin dose requirement (45)(46)(47)(48). Current knowledge about the genetic factors affecting other anticoagulants is more limited and this area requires future studies (46).…”

Section: Other Genetic Risk Factorsmentioning

confidence: 99%

Molecular Basis of Thrombophilia / MOLEKULARNE OSNOVE TROMBOFILIJE

Đorđević¹

2014

Journal of Medical Biochemistry

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SummaryThrombophilia is a multifactorial disorder, involving both genetic and acquired risk factors that affect the balance between procoagulant and anticoagulant factors and lead to increased thrombotic tendency. The severe forms of thrombophilia are caused by a deficiency of natural anticoagulants: antithrombin, protein C and protein S. The advances in DNA technology played an important role in the identification of the exact nature of these deficiencies and opened up new possibilities in genetic research and molecular diagnostics of thrombophilia. The major breakthrough came with the discovery of activated protein C resistance and the Factor V Leiden gene mutation. Shortly afterwards, a variant in the 3' untranslated region of the Factor II gene (FII G20210A) associated with an increased concentration of Factor II in plasma was described. These two gene variants represent the most common thrombophilic genetic risk factors. Recently, a novel prothrombin mutation (c.1787G>T) was identified in a Japanese family with juvenile thrombosis. This mutation leads to impaired inhibition of mutant thrombin by antithrombin, proposing a new mechanism of thrombophilia named resistance to antithrombin. In the last decade, se veral prothrombotic genetic risk factors have been described, including gene variants associated with defects of natural coagulation inhibitors, increased levels of coagulation factors or their impaired inhibition and defects of the fibrinolytic system. However, most of them are not of diagnostic value, due to their minor or unknown impact on the thrombotic risk. Large-scale DNA analysis systems are now becoming available, opening a new era in the genetic studies of the molecular basis of thrombophilia. Keywords: thrombophilia, genetic risk factors, gene variants Kratak sadr`ajTrombofilija nastaje kao rezultat kompleksne interakcije izme|u negeneti~kih i geneti~kih faktora rizika koji hemostaznu ravnote`u pomeraju u smeru hiperkoagulacije i dovode do pojave tromboze. Veoma zna~ajan faktor rizika za nastanak trombofilije je deficijencija inhibitora koagulacije: antitrombina, proteina C ili proteina S. Veliki korak u razu mevanju geneti~ke osnove i molekularne dijagnostike trombofilije napravljen je otkri}em rezistencije na aktivirani protein C i faktor V Leiden mutacije. Ubrzo je otkrivena i varijanta u 3'-nekodiraju}em regionu gena za faktor II (FII G20210A), za koju je pokazano da dovodi do povi{ene koncentracije protrombina u plazmi. Ove dve genske varijante su naju~estaliji geneti~ki faktori rizika za nastanak trombofilije. Nedavno je opisana nova mutacija u genu za protrombin (c.1787G >T) za koju je pokazano da dovodi do rezistencije na anti trombin, odnosno do smanjene mogu}nosti inaktivacije mu tira nog trombina od strane antitrombina, {to predstavlja novi mehanizam za nastanak trombofilije. U toku poslednjih decenija, opisan je veliki broj geneti~kih faktora rizika za nastanak trombofilije, uklju~uju}i one koji dovode do: nedos tatka inhibitora koagulacije, pove}anog nivoa ili smanjene inaktivacij...

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Relative contribution of CYP2C9 and VKORC1 genotypes and early INR response to the prediction of warfarin sensitivity during initiation of therapy

Cited by 78 publications

References 36 publications

Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement

Vitamin K antagonists in children with heart disease: height and VKORC1 genotype are the main determinants of the warfarin dose requirement

Prevalence of genetic polymorphisms of CYP2C9 and VKORC1 — Implications for warfarin management and outcome in Croatian patients with acute stroke

Molecular Basis of Thrombophilia / MOLEKULARNE OSNOVE TROMBOFILIJE

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