Plasma S/R ratio of warfarin co-varies with VKORC1 haplotype
2007 (English)In: Blood Coagulation & Fibrinolysis, ISSN 0957-5235 (print) 1473-5733 (online), Vol. 18, no 3, 293-296 p.Article in journal (Refereed) Published
We recently reported that the low-dose VKORC1*2 haplotype is an important genetic determinant for warfarin dose requirement and is associated with difficulties to attain stable therapeutic prothrombin time-International Normalized Ratio in patients undergoing anticoagulation therapy. The aim of this study was to investigate whether patients with VKORC1*2 compared with patients carrying high-dose haplotypes VKORC1*3 or VKORC1*4 had different warfarin S/R ratios in their plasma, and whether that was related to CYP2C9 variants CYP2C9*2 and CYP2C9*3 or other factors. Samples from patients previously haplotyped for VKORC1 and measured for plasma warfarin concentration were genotyped for the CYP2C9 variants CYP2C9*2 and CYP2C9*3. Nonparametric statistical analysis was performed to elucidate whether there was any significant difference in the warfarin S/R ratio between the two patient groups. Our result shows that there is a significant difference (P < 0.01) in warfarin S/R ratios between VKORC1*2 and VKORC1*3 or VKORC1*4 patients. This difference did not originate from CYP2C9 variants CYP2C9*2 and CYP2C9*3. We speculate that VKORC1 haplotypes possibly are linked to some unidentified factors involved in the metabolic clearance of warfarin enantiomers. Dose-dependent variations in (S)-warfarin and (R)-warfarin clearance in these patients can also be a probable explanation for the difference in warfarin S/R ratios.
Place, publisher, year, edition, pages
2007. Vol. 18, no 3, 293-296 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-14489OAI: oai:DiVA.org:liu-14489DiVA: diva2:23584