In the latest clinical study on warfarin pharmacogenetics, included in this issue from University of Utah clinician scientists, McMillin and her colleagues take a closer look at gene-based warfarin doseing compared to standard care practices in orthopedic surgery. The primary purpose is laudable-compare gene-based with standard, non-gene based warfarin dosing in total hip or knee arthroplasty.The short duration of the trial means the ability to use genomic information to examine stability of warfarin dosing over time is limited. Two weeks of warfarin therapy is unlikely sufficient to judge the overall occurrence of adverse effects from the drag, particularly those that occur with longer anticoagulation periods (post-DVT for example). This is a major limitation in determining the utility of gene-based dosing but is appropriately discussed in the accompanying paper. An important finding from this paper is that it may be that the lack of genetic markers means more aggressive therapy to achieve a therapeutic INR is made more possible and safer. Much remains to be understood in pharmacogenetic applications. More work is necessary to fully characterize genetic variants including the contribution of at risk alleles and whether there are additive or even synergistic effects with greater numbers of these alleles. It is also unknown which variants are most predictive of serious adverse outcome versus milder reactions that can be easilv manaeed clinicallv. This information may also come with future clinical research.
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