The Effect of Gene-Obesity and Gene-Care Setting Interactions on Risk of Major Bleeding Events in Warfarin Users

Thesis (Master's)--University of Washington, 2014A commonly prescribed anticoagulant, Warfarin (Coumadin®), reduces thromboembolic (blood clotting) event rates in patients with atrial fibrillation, stroke, joint replacement, and other conditions that present increased clotting risk. Unfortunately, pharmacogenetic-guided dosing algorithms have not yielded the predicted effect clinicians and researchers anticipated compared to using the clinically guided dosing methods. Further explanations for effects modifying the genetic effects present on bleeding risk in warfarin patients are warranted. We analyzed a case-control study to investigate gene-environment interaction effects on risk of serious bleeding in warfarin users in a community setting. No interaction was found between CYP2C9/VKORC1 and obesity. A statistically significant interaction was found between CYP4F2 x obesity, however, the p-value of 0.049 would not hold its statistical significance to Bonferroni correction for multiple comparisons. No statistically significant interaction was found between CYP2C9/VKORC1 x care setting or between CYP4F2 x care setting. These findings need to be validated in a larger population to inform future clinical guidelines in order for warfarin users to receive the optimal benefit