Plasma S/R ratio of warfarin co-varies with VKORC1 haplotype

Osman, Abdimajid (author): Östergötlands Läns Landsting,Linköpings universitet,Klinisk kemi,Hälsouniversitetet

Enström, Camilla (author): Linköpings universitet,Institutionen för biomedicin och kirurgi,Hälsouniversitetet

Lindahl, Tomas (author): Östergötlands Läns Landsting,Linköpings universitet,Klinisk kemi,Hälsouniversitetet

(creator_code:org_t)

2007
2007
English.
In: Blood Coagulation and Fibrinolysis. - 0957-5235 .- 1473-5733. ; 18:3, s. 293-296

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

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