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VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation.
Clin Pharmacol Ther. 2006 Jul; 80(1):13-22.CP

Abstract

OBJECTIVE

Our objective was to assess the effects of VKORC1 and CYP2C9 genotypes on severe overanticoagulation and time to achieve stability and their contributions to dose requirement during the initial phase of acenocoumarol treatment.

METHODS

A prospective follow-up study was conducted at 2 anticoagulation clinics in The Netherlands. We assessed the CYP2C9 genotype (CYP2C9*2 and CYP2C9*3 polymorphisms) and the VKORC1 C1173T genotype of the subjects and collected data on international normalized ratio, dose, comedication, and comorbidity.

RESULTS

Of the 231 patients in the cohort, 150 (64.9%) had a VKORC1 C1173T polymorphism and 84 (36.4%) had a CYP2C9*2 or CYP2C9*3 allele. Only carriers of a combination of a CYP2C9 polymorphism and a VKORC1 polymorphism had an increased risk of severe overanticoagulation compared with subjects with no polymorphism or only 1 polymorphism (hazard ratio, 3.83 [95% confidence interval, 1.62-9.05]). The time to achieve stability was associated with the possession of the CYP2C9 genotype, not with the VKORC1 genotype (hazard ratio for CYP2C9*3 allele compared with CYP2C9 wild type, 0.59 [95% confidence interval, 0.40-0.87]). Patients with a VKORC1 polymorphism required significantly lower doses than VKORC1 CC wild-type patients. A larger part of the variability in dose requirement was explained by the VKORC1 genotype than by the CYP2C9 genotype (21.4% and 4.9%, respectively).

CONCLUSION

Being a carrier of a combination of polymorphisms of VKORC1 and CYP2C9, rather than of one of these polymorphisms, is associated with severe overanticoagulation. The time to achieve stability is mainly associated with the CYP2C9 genotype.

Authors+Show Affiliations

Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. t.schalekamp@pharm.uu.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16815313

Citation

Schalekamp, Tom, et al. "VKORC1 and CYP2C9 Genotypes and Acenocoumarol Anticoagulation Status: Interaction Between Both Genotypes Affects Overanticoagulation." Clinical Pharmacology and Therapeutics, vol. 80, no. 1, 2006, pp. 13-22.
Schalekamp T, Brassé BP, Roijers JF, et al. VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation. Clin Pharmacol Ther. 2006;80(1):13-22.
Schalekamp, T., Brassé, B. P., Roijers, J. F., Chahid, Y., van Geest-Daalderop, J. H., de Vries-Goldschmeding, H., van Wijk, E. M., Egberts, A. C., & de Boer, A. (2006). VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation. Clinical Pharmacology and Therapeutics, 80(1), 13-22.
Schalekamp T, et al. VKORC1 and CYP2C9 Genotypes and Acenocoumarol Anticoagulation Status: Interaction Between Both Genotypes Affects Overanticoagulation. Clin Pharmacol Ther. 2006;80(1):13-22. PubMed PMID: 16815313.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation. AU - Schalekamp,Tom, AU - Brassé,Bjorn P, AU - Roijers,Janine F M, AU - Chahid,Youssef, AU - van Geest-Daalderop,Johanna H H, AU - de Vries-Goldschmeding,Hanneke, AU - van Wijk,Eduard M, AU - Egberts,Antoine C G, AU - de Boer,Anthonius, PY - 2006/01/10/received PY - 2006/04/11/accepted PY - 2006/7/4/pubmed PY - 2006/8/4/medline PY - 2006/7/4/entrez SP - 13 EP - 22 JF - Clinical pharmacology and therapeutics JO - Clin. Pharmacol. Ther. VL - 80 IS - 1 N2 - OBJECTIVE: Our objective was to assess the effects of VKORC1 and CYP2C9 genotypes on severe overanticoagulation and time to achieve stability and their contributions to dose requirement during the initial phase of acenocoumarol treatment. METHODS: A prospective follow-up study was conducted at 2 anticoagulation clinics in The Netherlands. We assessed the CYP2C9 genotype (CYP2C9*2 and CYP2C9*3 polymorphisms) and the VKORC1 C1173T genotype of the subjects and collected data on international normalized ratio, dose, comedication, and comorbidity. RESULTS: Of the 231 patients in the cohort, 150 (64.9%) had a VKORC1 C1173T polymorphism and 84 (36.4%) had a CYP2C9*2 or CYP2C9*3 allele. Only carriers of a combination of a CYP2C9 polymorphism and a VKORC1 polymorphism had an increased risk of severe overanticoagulation compared with subjects with no polymorphism or only 1 polymorphism (hazard ratio, 3.83 [95% confidence interval, 1.62-9.05]). The time to achieve stability was associated with the possession of the CYP2C9 genotype, not with the VKORC1 genotype (hazard ratio for CYP2C9*3 allele compared with CYP2C9 wild type, 0.59 [95% confidence interval, 0.40-0.87]). Patients with a VKORC1 polymorphism required significantly lower doses than VKORC1 CC wild-type patients. A larger part of the variability in dose requirement was explained by the VKORC1 genotype than by the CYP2C9 genotype (21.4% and 4.9%, respectively). CONCLUSION: Being a carrier of a combination of polymorphisms of VKORC1 and CYP2C9, rather than of one of these polymorphisms, is associated with severe overanticoagulation. The time to achieve stability is mainly associated with the CYP2C9 genotype. SN - 0009-9236 UR - https://www.unboundmedicine.com/medline/citation/16815313/VKORC1_and_CYP2C9_genotypes_and_acenocoumarol_anticoagulation_status:_interaction_between_both_genotypes_affects_overanticoagulation_ L2 - https://doi.org/10.1016/j.clpt.2006.04.006 DB - PRIME DP - Unbound Medicine ER -