Population variation in VKORC1 haplotype structure

Marsh, Sharon; King, Cristi R.; Porche-Sorbet, Rhonda; Scott-Horton, Tiffany; Eby, Charles S.

doi:10.1111/j.1538-7836.2006.01759.x

Cited by 51 publications

(23 citation statements)

References 8 publications

(30 reference statements)

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“…The prevalence of these genotypes differed by race and contributed to lower warfarin doses in Asian and Mexican populations and the greater doses in African ancestry populations. 55,56 The 6853 SNP correlated with greater gene expression of vitamin K epoxide reductase activity suggesting that carriers of the G allele require greater warfarin doses because they have greater endogenous epoxide activity.…”

Section: Snps In Vkorc1 Correlate With Warfarin Dosementioning

confidence: 99%

Pharmacogenetics-Based Coumarin Therapy

Gage¹

2006

Hematology

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To reduce the risk of hemorrhage, experts advocate prescribing the anticipated therapeutic dose to patients who are beginning coumarin therapy, but until now there was no accurate way to estimate that dose. Using pharmacogenetics-based coumarin therapy, clinicians can now estimate the therapeutic dose by genotyping their patients for single nucleotide polymorphisms (SNPs) that affect coumarin metabolism or sensitivity. SNPs in the cytochrome P450 complex (CYP2C9) affect coumarin metabolism. Patients with either of two common variants, CYP2C9*2 or CYP2C9*3, metabolize coumarins slowly and are twice as likely to have a laboratory or clinical adverse event, unless their initial coumarin doses are reduced. SNPs in vitamin K epoxide reductase (VKORC1) correlate with coumarin sensitivity. Patients known to be homozygous for a common VKORC1 promoter polymorphism, −1639 G>A (also designated as VKOR 3673, haplotype A, or haplotype*2), should be started on lower coumarin doses than genotype GG patients. By providing an estimate of the therapeutic coumarin dose, pharmacogenetics-based therapy may improve the safety and effectiveness of coumarin therapy.

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Section: Snps In Vkorc1 Correlate With Warfarin Dosementioning

confidence: 99%

Pharmacogenetics-Based Coumarin Therapy

Gage¹

2006

Hematology

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“…Response to warfarin may vary by race for several reasons, including cultural differences in dietary habits and healthcare beliefs and inter-racial differences in CYP2C9 and VKORC1 genotype distribution [7,9,10]. The objective of this study was to identify factors that contribute to unstable anticoagulation after achieving initial dose stabilization among African Americans receiving chronic warfarin therapy.…”

Section: Introductionmentioning

confidence: 98%

Predictors of unstable anticoagulation in African Americans

Cavallari

Aston

Momary

et al. 2008

J Thromb Thrombolysis

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We conclude that poor warfarin adherence and gastrointestinal illness are major contributors to unstable anticoagulation in African Americans. Our data suggest that, similar to Caucasians, improving warfarin adherence rates may be an important mean to improve anticoagulation control in African Americans. In addition, close monitoring during acute illness may be particularly important in this population.

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“…7,[17][18][19][20] However, failure to select the functionally relevant SNP could reduce the predictive value of VKORC1 genotyping in ethnic populations with lower LD of the 5 haplotype-defining SNPs. [21][22][23] The 5-SNP haplotype A is common in Chinese (87%) and Malays (65%), 23 whereas haplotype B prevails in European Americans (64%) 11 and Indians (82%). 23 Although all 5 SNPs are generally in strong LD in white and Asian populations, haplotype structures are more diverse in African populations (data from HapMap 24 ).…”

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confidence: 99%