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Personalized Warfarin Dosing Enhanced by MS-Based SNP Genotyping

The anticoagulant drug warfarin (also known under the brand name Coumadin) is commonly used to prevent blood clots and embolisms. However, the drug exhibits significant inter-individual variability in dosing requirements. This variability is partly due to single nucleotide polymorphisms (SNPs) that influence either drug action or drug metabolism. Rapid genotyping of these SNPs helps clinicians to choose appropriate initial doses to quickly achieve anticoagulation effects and to prevent complications. A group led by Dr. Haifeng Wu of Ohio State University has developed a new, rapid method to genotype SNPs that will help clinicians to choose appropriate doses of warfarin for individual patients. Using surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF MS), which can determine the elemental composition of a sample, the researchers were able to determine the genotype of three warfarin-related SNPs (CYP2C9*2, CYP2C9*3, and VKORC1 3673G>A) in under five hours with high levels of accuracy. The researchers suggested that "on-site application of this method in hospital laboratories will greatly help clinicians to determine appropriate doses of warfarin to treat patients with thromboembolic disorders." In future studies, the Ohio State scientists plan to apply the SELDI-TOF platform to genotype other medically important SNPs that influence the efficacy and safety profiles of many drug therapies and to thus ultimately promote personalized health care. This work was reported in the March issue of the Journal of Molecular Diagnostics. [Press release] [Journal of Molecular Diagnostics abstract]