Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose.

By Mark J. Rieder, A. Reiner, B. Gage, Deborah A. Nickerson, C. Eby, Howard L. McLeod, David K. Blough, K. Thummel, D. Veenstra, A. Rettie. New England Journal of Medicine, 2005

1,436 citations recorded by the source corpus.

Subfields: Biochemistry, Cardiology and Cardiovascular Medicine, Pharmacology

View Paper: https://www.semanticscholar.org/paper/4ac01842188408c5733b37501c4031ee56daa881

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biochemistry

1. M. Schwab
2. Ulrich M. Zanger

In Cardiology and Cardiovascular Medicine

1. Aldons J. Lusis
2. Cynthia Rudin

In Pharmacology

1. M. Schwab
2. Ulrich M. Zanger

Citations in the corpus

• Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. (2013, background): “In a study of 539 white patients on steady-state warfarin therapy 9% of variability in warfarin dose could be explained by CYP2C9 variants, compared to 25% by variants of VKORC1 (Rieder et al., 2005).”
• Genotypes of the cytochrome p450 isoform, CYP2C9, and the vitamin K epoxide reductase complex subunit 1 conjointly determine stable warfarin dose: a prospective study (2006, background): “In that study, the haplotypes associated with the highest warfarin dose all carried the 1173 C allele [13].”
• Mapping the Genetic Architecture of Gene Expression in Human Liver (2008, background): “For example, VKORC1 , a gene recently associated with warfarin dosing [24], has liver gene expression values that are significantly associated with an eSNP near the 3 9 end of the gene ( p ¼ 1.66 3 10 (cid:2) 23 ).”
• A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose (2009, background): “In prior fine-mapping of the VKORC1 locus [8], we identified rs9923231 as one of three SNPs located in introns or immediately flanking VKORC1 that exhibit almost perfectly concordant genotypes yielding pairwise linkage disequilibrium (LD) r(2)<1 and which define the warfarin-sensitive A-T-T haplotyp”
• A Regulatory Science Perspective on Warfarin Therapy: A Pharmacogenetic Opportunity (2009, background): “This mutation is in linkage disequilibrium with other mutations, and the haplotypes are now well defined.(14) Since the discovery of VKORC1 and its variants, clinical studies evaluating the impact of the VKORC1 gene on warfarin dose requirements have been widely published.”
• Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin dosing: 2017 Update (2017, background): “The –1639G>A polymorphism is present on a haplotype that affects VKORC1 protein expression (VKORC1 allele definition table(19)).(18) Other common VKORC1 SNPs or haplotypes do not further improve warfarin dose prediction.”
• Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). (2008, background): “Joffe et al, 196 also studying CYP2C9 SNPs, found an upward trend in rates of an INR (cid:4) 6.0 or of bleeding in patients who were categorized as heterozygotes or compound hetero/homozygotes compared to wild types, as did Veenstra et al. 34 A similar increased risk of bleeding was seen in patients”