Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders
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Coumarin resistance

Increased sensitivity or resistance to vitamin K antagonists can be caused by various genetic variations in distinct genes.

Systematic

Genetic alterations of drug tolerance
Coumarin resistance
CYP2A6
CYP2C9
CYP4F2
VKORC1
Disturbances of cytochrome p450 system
Hepatitis C response to therapy
PPI-induced Hypomagnesemia

References:

1.

Wood AW et al. (1974) Genetic variation in coumarin hydroxylase activity in the mouse (Mus musculus).

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2.

Whitlon DS et al. (1978) Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition.

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3.

Greavses JH et al. (1967) Heritable resistance to warfarin in rats.

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4.

Lewis RJ et al. (1967) Warfarin resistance.

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5.

Pool JG et al. (1968) Warfarin resistance in the rat.

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6.

None (1970) The second reported kindred with hereditary resistance to oral anticoagulant drugs.

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7.

Vesell ES et al. (1968) Genetic control of dicumarol levels in man.

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8.

Alving BM et al. (1985) Hereditary warfarin resistance. Investigation of a rare phenomenon.

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9.

Nebert DW et al. () The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature.

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10.

Takeuchi F et al. (2009) A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose.

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11.

Borgiani P et al. (2009) CYP4F2 genetic variant (rs2108622) significantly contributes to warfarin dosing variability in the Italian population.

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12.

Limdi NA et al. (2008) VKORC1 polymorphisms, haplotypes and haplotype groups on warfarin dose among African-Americans and European-Americans.

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13.

Cooper GM et al. (2008) A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose.

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14.

Takahashi H et al. (2006) Different contributions of polymorphisms in VKORC1 and CYP2C9 to intra- and inter-population differences in maintenance dose of warfarin in Japanese, Caucasians and African-Americans.

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15.

Rost S et al. (2004) Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2.

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16.

Shikata E et al. (2004) Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and gamma-glutamyl carboxylase) gene variants with warfarin sensitivity.

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17.

O'REILLY RA et al. (1964) HEREDITARY TRANSMISSION OF EXCEPTIONAL RESISTANCE TO COUMARIN ANTICOAGULANT DRUGS. THE FIRST REPORTED KINDRED.

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18.

Lindberg RL et al. (1992) Molecular characterization of the murine Coh locus: an amino acid difference at position 117 confers high and low coumarin 7-hydroxylase activity in P450coh.

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19.

Yuan HY et al. (2005) A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity.

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20.

Caldwell MD et al. (2008) CYP4F2 genetic variant alters required warfarin dose.

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21.

et al. (2009) Estimation of the warfarin dose with clinical and pharmacogenetic data.

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22.

Kohn MH et al. (2000) A gene-anchored map position of the rat warfarin-resistance locus, Rw, and its orthologs in mice and humans.

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23.

Lush IE et al. (1978) Genetic variation between mice in their metabolism of coumarin and its derivatives.

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24.

Yamano S et al. (1990) The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes.

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25.

OMIM.ORG article

Omim 122700 external link
Update: Aug. 14, 2020
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