The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
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
Open accessAbstract
OBJECTIVE: To investigate pharmacokinetic and pharmacodynamic factors associated with population differences in warfarin doses needed to achieve anticoagulation, in particular the possible involvement of genetic variability in vitamin K epoxide reductase (VKOR) and CYP2C9. METHODS: Warfarin maintenance dose, unbound plasma S-warfarin concentration [Cu(S)] and INR were determined in 157 Caucasians, 172 Japanese, and 36 African-Americans stably anticoagulated patients. In a subset (n = 166), fully carboxylated plasma normal prothrombin levels (NPT) were also measured. Genotyping for seven CYP2C9 (CYP2C9*1 through 6 and *11) and seven VKORC1 variants were performed in 115 Caucasians and 64 Japanese patients and 66 healthy African-Americans. Multivariate analysis was performed to identify covariates associated with warfarin requirement. RESULTS: The relationship between NPT and Cu(S) indicated Japanese are more susceptible to inhibition of NPT production by S-warfarin than the other two populations. VKORC1 1173 C > T had a greater frequency in Japanese (89.1%) than Caucasians (42.2%) and African-Americans (8.6%). CYP2C9 variants with reduced metabolizing ability were less frequent in Japanese compared to the other two populations. The median warfarin dose was significantly higher in Caucasians than Japanese patients (5.5 versus 3.5 mg/day), however, when matched for CYP2C9*1 homozygosity, no difference in dose was observed between VKORC1 genotype-matched groups. Furthermore, VKORC1 1173C > T and CYP2C9 (*2/*3/*11) genotypes, age and weight were identified as independent covariates contributing to interpatient variability in warfarin dosage. CONCLUSIONS: Both VKORC1 and CYP2C9 polymorphisms contribute to inter-population difference in warfarin doses among the three populations, but their contribution to intra-population variability may differ within each population.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Due to genetic differences in pharmacokinetics and pharmacodynamics, clopidogrel [29], phenytoin [30], warfarin [31], clozapine [32], and carbamazepine [33] also had variable efficacy and side-effect profiles in Western and non-Western individuals.”
From Hasty generalizations and generics in medical research: A systematic review (2024) · cites this paper as [31]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Pharmacology and Management of the Vitamin K Antagonists
Ansell, J., Hirsh, J., Poller, L., Bussey, H. I., Jacobson, A. K., & Hylek, E. M. (2004) · CHEST Journal · doi:10.1378/chest.126.3_suppl.204s · Cited by 1,530
Effect of VKORC1 Haplotypes on Transcriptional Regulation and Warfarin Dose
Rieder, M. J., Reiner, A. P., Gage, B. F., Nickerson, D. A., Eby, C. S., McLeod, H. L., Blough, D. K., Thummel, K. E., Veenstra, D. L., & Rettie, A. E. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa044503 · Cited by 1,391
Aithal, G. P., Day, C. P., Kesteven, P. J., & Daly, A. K. (1999) · The Lancet · doi:10.1016/s0140-6736(98)04474-2 · Cited by 1,239
Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2
Rost, S., Fregin, A., Ivaškevičius, V., Conzelmann, E., Hörtnagel, K., Pelz, H., Lappegård, K. T., Seifried, E., Scharrer, I., Tuddenham, E. G. D., et al. (2004) · Nature · doi:10.1038/nature02214 · Cited by 1,152
Higashi, M. K. (2002) · JAMA · doi:10.1001/jama.287.13.1690 · Cited by 1,052
D’Andrea, G., D’Ambrosio, R., Perna, P. D., Chetta, M., Santacroce, R., Brancaccio, V., Grandone, E., & Margaglione, M. (2004) · Blood · doi:10.1182/blood-2004-06-2111 · Cited by 696
Yuan, H., Chen, J., Lee, M. T. M., Wung, J., Chen, Y., Charng, M., Lu, M.-J., Hung, C., Wei, C.-Y., Chen, C.-H., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi180 · Cited by 484
Common VKORC1 and GGCX polymorphisms associated with warfarin dose
Wadelius, M., Chen, L. Y., Downes, K., Ghori, J., Hunt, S. E., Eriksson, N., Wallerman, O., Melhus, H., Wadelius, C., Bentley, D. R., et al. (2005) · The Pharmacogenomics Journal · doi:10.1038/sj.tpj.6500313 · Cited by 462
Bodin, L. (2005) · Blood · doi:10.1182/blood-2005-01-0341 · Cited by 360
Scordo, M. G. (2002) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2002.129321 · Cited by 344
Self-citation
Cited by
Sorted by citations
Estimation of the Warfarin Dose with Clinical and Pharmacogenetic Data
The International Warfarin Pharmacogenetics Consortium (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0809329 · Cited by 1,573
Anderson, J. L., Horne, B. D., Stevens, S. M., Grove, A. S., Barton, S., Nicholas, Z. P., Kahn, S. F. S., May, H. T., Samuelson, K. M., Muhlestein, J. B., et al. (2007) · Circulation · doi:10.1161/circulationaha.107.737312 · Cited by 723
Pena, S. D. J., Pietro, G. D., Fuchshuber-Moraes, M., Genro, J. P., Hutz, M. H., Kehdy, F. S. G., Kohlrausch, F. B., Magno, L. A. V., Montenegro, R. C., de Moraes, M. O., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017063 · Cited by 678
Shen, A. Y., Yao, J. F., Brar, S. S., Jorgensen, M. B., & Chen, W. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.01.098 · Cited by 657
Genetic Determinants of Response to Warfarin during Initial Anticoagulation
Schwarz, U. I., Ritchie, M. D., Bradford, Y., Li, C., DUDEK, S. M., Frye-Anderson, A., Kim, R. B., Roden, D. M., & Stein, C. M. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0708078 · Cited by 572
Self-citation
Metadata
- Authors
- Takahashi, H., Wilkinson, G. R., Nutescu, E. A., Morita, T., Ritchie, M. D., Scordo, M. G., Pengo, V., Barban, M., Padrini, R., Ieiri, I., Otsubo, K., Kashima, T., Kimura, S., Kijima, S., & Echizen, H.
- Affiliations
- Meiji Pharmaceutical University (JP)
- University of Illinois Chicago (US)
- Vanderbilt University (US)
- University of Messina (IT)
- University of Padua (IT)
- Tottori University (JP)
- Eisai (Japan) (JP)
- Corresponding author
- Takahashi, Harumi
- ORCID
- Venue
- Pharmacogenetics and Genomics
- Published
- 2006-02
- Volume
- 16
- Issue
- 2
- Pages
- 101-110
- ISSN
- 1744-6872 (ISSN-L)
- OpenAlex
- W2042292509
- Cited by
- 376
- References
- 31
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 10 · 2019: 17 · 2018: 9 · 2017: 14 · 2016: 16 · 2015: 16 · 2014: 28 · 2013: 25 · 2012: 25
- FWCI
- 38.09
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Pharmacogenetics and Genomics (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, other-oa)
- Funders
- Eisai
- National Institutes of Health (GM31304)
- U.S. Public Health Service
- National Institute of General Medical Sciences (GM31304, P01GM031304)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- warfarin, VKORC1, CYP2C9, genetic polymorphism, vitamin K epoxide reductase, interpopulation variability, Japanese, Caucasians, African Americans, S-warfarin, anticoagulation, pharmacogenetics
- MeSH terms
- Aryl Hydrocarbon Hydroxylases, Black or African American, Female, Genotype, Humans, Mixed Function Oxygenases, Infant, Japan, Male, Pharmacogenetics, United States, Genetic Variation, Warfarin, Black People, White People, Asian People, Vitamin K Epoxide Reductases, Cytochrome P-450 CYP2C9
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
