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GENETIC POLYMORPHISMS OF VKORC1 ©2010 Pharmacology Weeky Inc
Allele	Population	Single Nucleotide Polymorphism	Location	VKORC1 Activity	VKORC1 Expression
VKORC1	General Population	Wild-type; 5,139bp	16p11.2	normal	normal
VKORC12*	10.6% African Americans 36-45% European-Americans 87-94% Asians	C6484T (1173C/T)	Intron 1	↓	↓ mRNA
VKORC12*	10.9% African Americans 36-42% European-Americans 87-93% Asians	G3673A (-1639G/A)	Promoter	↓	↓ mRNA
VKORC13*	52% African Americans 33-39% European-Americans 8-17% Asians	G9041A (3730G/A)	3'UTR	↑	↑ mRNA
VKORC13*	20% African Americans 0.5% Germans	C8773T	Exon 3	↑	↑ mRNA
VKORC14*	10% African Americans 20% Europeans 2% Asians	C6009T	Intron	↑	↑ mRNA

The letters before and after the numbers represent the single nucleotides that make up the DNA sequence and codons to code for an amino acid (A = adenine, C = cytosine, G = guanine, T = thymine). 3'UTR = three prime untranslated region

Medications Affected:

Warfarin (Coumadin, Jantoven)

Pharmacology Weekly VKORC1 Related Publications:

Busti AJ, Lehew DS, Daves BJ, McKeever GC. How do known genetic polymorphisms to VKORC1 influence the safety and efficacy of warfarin (Coumadin, Jantoven)? PW Pharmacogenet Newsl 2009;1(8):1-4. Link to Answer

References for Table:

Rost S. Fregin A. Ivaskevicius V et al. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 2004;427:537-541. PubMed

Sconce EA, Khan TI, Wynne HA et al. The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen. Blood 2005;106:2329-33. PubMed

Reitsma PH, van der Heijden JF et al. A C1173T dimorphism in the VKORC1 gene determines coumarin sensitivity and bleeding risk. PLoS Med 2005;2:e312. PubMed

Limdi NA, Arnett DK, Goldstein JA, et al. Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European-Americans and African-Americans. Pharmacogenomics 2008;9:511-26. PubMed

Schelleman H, Chen Z, Kealey C, et al. Warfarin response and vitamin K epoxide reductase complex 1 in African Americans and Caucasians. Clin Pharmacol Ther 2007;81:742-7. PubMed

Limdi N, McGwin G, Goldstein J, et al. Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin. Clin Pharmacol Ther 2008;83:312-21. PubMed

Kimura R, Miyashita K, Kokubo Y et al. Genotypes of vitamin K epoxide reductase, gamma-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients. Thromb Res 2007;120:181-6. PubMed

Obayashi K, Nakamura K, Kawana J et al. VKORC1 gene variations are the major contributors of variation in warfarin dose in Japanese patients. Clin Pharmacol Ther 2006;80:169-78. PubMed

D'Andrea G, D'Ambrosio RL, Di Perna P et al. A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. Blood 2005;105:645-9. PubMed

Herman D, Petemel P, Stegnar M et al. The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement. Thromb Haemost 2006;95:782-7. PubMed

Takahashi H, Wilkinson GR, Nutescu EA et al. 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. Pharmacogenet Genomics 2006;16:101-10. PubMed

Geisen C, Watzka M, Sittinger K et al. VKORC1 haplotypes and their impact on the inter-individual and inter-ethnical variability of oral anticoagulation. Thromb Haemost 2005;94:773-9. PubMed

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