The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements
Abstract
INTRODUCTION: The primary objective of this study was to determine whether variability in warfarin dose requirements is determined by common polymorphisms in genes whose products are involved in the pharmacodynamics and pharmacokinetics of warfarin, namely, the coagulation factors, vitamin K epoxide reductase complex subunit 1 (VKORC1), and cytochrome P450 (CYP) 2C9. METHODS: Patients (N = 350) receiving stable doses of warfarin at 3 consecutive visits were enrolled, and a deoxyribonucleic acid sample was collected. Samples were genotyped for polymorphisms in the factor II, factor VII, factor X, VKORC1, and CYP2C9 genes. A stepwise linear regression analysis was used to determine the independent effects of genetic and nongenetic factors on mean warfarin dose requirements. RESULTS: Variables associated with lower warfarin dose requirements were VKORC1 3673 AA genotype (P < .0001), VKORC1 3673 GA genotype (P < .0001), 1 variant CYP2C9 allele (P < .0001), 2 variant CYP2C9 alleles (P = .0004), increasing age (P = .0005), concomitant CYP2C9 inhibitors (P = .0005), and goal international normalized ratio (P = .01). Variables associated with higher warfarin dose requirements were weight (P < .0001), current smoker status (P = .0009), mean international normalized ratio (P = .001), concomitant CYP2C9 inducers (P = .006), factor X insertion/deletion genotype (P = .01), factor X insertion/insertion genotype (P = .04), factor VII deletion/deletion genotype (P = .04), and calculated vitamin K intake (P = .05). The linear regression model explained 51.4% of the variability in warfarin dose requirements. CONCLUSION: Polymorphisms in warfarin drug target and metabolizing enzyme genes, in addition to nongenetic factors, were important determinants of warfarin dose requirements.
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Cites
Oral Anticoagulants: Mechanism of Action, Clinical Effectiveness, and Optimal Therapeutic Range
Hirsh, J., Dalen, J. E., Anderson, D. R., Poller, L., Bussey, H., Ansell, J., & Deykin, D. (2001) · Chest · doi:10.1378/chest.119.1_suppl.8s · Cited by 1,804
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 1,399
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 1,243
Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2
Rost, S., Fregin, A., Ivaskevicius, V., Conzelmann, E., Hörtnagel, K., Pelz, H.-J., Lappegard, K., Seifried, E., Scharrer, I., Tuddenham, E. G. D., et al. (2004) · Nature · doi:10.1038/nature02214 · Cited by 1,134
Higashi, M. K. (2002) · JAMA · doi:10.1001/jama.287.13.1690 · Cited by 1,048
Sconce, E. A., Khan, T. I., Wynne, H. A., Avery, P., Monkhouse, L., King, B. P., Wood, P., Kesteven, P., Daly, A. K., & Kamali, F. (2005) · Blood · doi:10.1182/blood-2005-03-1108 · Cited by 947
Identification of the gene for vitamin K epoxide reductase
Li, T., Chang, C.-Y., Jin, D.-Y., Lin, P.-J., Khvorova, A., & Stafford, D. W. (2004) · Nature · doi:10.1038/nature02254 · Cited by 707
D'Andrea, G., D'Ambrosio, R. L., Di Perna, P., Chetta, M., Santacroce, R., Brancaccio, V., Grandone, E., & Margaglione, M. (2005) · Blood · doi:10.1182/blood-2004-06-2111 · Cited by 699
Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data
Lee, C. R., Goldstein, J. A., & Pieper, J. A. (2002) · Pharmacogenetics · doi:10.1097/00008571-200204000-00010 · Cited by 686
Yuan, H.-Y., Chen, J.-J., Lee, M. T. M., Wung, J.-C., Chen, Y.-F., Charng, M.-J., Lu, M.-J., Hung, C.-R., Wei, C.-Y., Chen, C.-H., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi180 · Cited by 486
Cited by
A genome-wide scan for common genetic variants with a large influence on warfarin maintenance dose
Cooper, G. M., Johnson, J. A., Langaee, T. Y., Feng, H., Stanaway, I. B., Schwarz, U. I., Ritchie, M. D., Stein, C. M., Roden, D. M., Smith, J. D., et al. (2008) · Blood · doi:10.1182/blood-2008-01-134247 · Cited by 481
Self-citation
Metadata
- Authors
- AQUILANTE, C., LANGAEE, T., LOPEZ, L., YARANDI, H., TROMBERG, J., MOHUCZY, D., GASTON, K., WADDELL, C., CHIRICO, M., & JOHNSON, J.
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2006-04
- Volume
- 79
- Issue
- 4
- Pages
- 291-302
- ISSN
- 0009-9236 (ISSN-L)
- OpenAlex
- W2170483665
- Cited by
- 266
- References
- 31
- FWCI
- 27.40
- Type
- journal article
- Language
- en
- Open access
- closed
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- AQUILANTE, C., LANGAEE, T., LOPEZ, L., YARANDI, H., TROMBERG, J., MOHUCZY, D., GASTON, K., WADDELL, C., CHIRICO, M., & JOHNSON, J. (2006). Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements. Clinical Pharmacology & Therapeutics. https://doi.org/10.1016/j.clpt.2005.11.011
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