Lund, K., Gaffney, D., Spooner, R., Etherington, A. M., Tansey, P. and Tait, R. C. (2012) Polymorphisms in VKORC1 have more impact than CYP2C9 polymorphisms on early warfarin International Normalized Ratio control and bleeding rates. British Journal of Haematology, 158(2), pp. 256-261. (doi: 10.1111/j.1365-2141.2012.09150.x) (PMID:22571356)
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Abstract
Poor warfarin control with resultant high International Normalized Ratios (INRs) and bleeding events is most common during the first months of treatment. The effects of genetic polymorphisms at the vitamin K epoxide reductase [VKORC1] and cytochrome P450 2C9 [CYP2C9] loci have been increasingly acknowledged as contributory factors of enhanced warfarin sensitivity. In our prospective, blinded study, 557 patients (49·1% male, mean age 65·4 years, range 18–91 years) commencing warfarin (target INR 2·5) were genotyped and monitored through the first 3 months of anticoagulation. Homozygosity for the −1639 G>A single nucleotide functional promoter polymorphism of the VKORC1 gene (genotype AA; 14·5% of cases) was associated with a significantly shortened time to therapeutic INR ≥ 2 (P < 0·01), reduced stable warfarin dose (P < 0·01), and an increased number of INRs > 5 (P < 0·001) and occurrence of bleeding events (P < 0·01) during the first month, as compared to the GG genotype. CYP2C9 genetic variations *2 and *3 were not associated with significant effect on these factors. Neither VKORC1 nor CYP2C9 polymorphisms influenced these parameters beyond the first month of treatment. These findings imply possible benefits of assessing VKORC1 polymorphisms prior to anticoagulation, particularly as a low dose induction regime in VKORC1 AA individuals appears to reduce the incidence of high INRs.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Tait, Dr Robert and Lund, Dr Kirstin and Gaffney, Dr Dairena |
| Authors: | Lund, K., Gaffney, D., Spooner, R., Etherington, A. M., Tansey, P., and Tait, R. C. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
| Journal Name: | British Journal of Haematology |
| Publisher: | Wiley |
| ISSN: | 0007-1048 |
| ISSN (Online): | 1365-2141 |
| Published Online: | 10 May 2012 |
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