![]() ![]() However, all the available technologies require initial DNA extraction from blood and take a minimum of 3 to 4 h for the PCR step to be completed. In general, studies comparing the validity of the various methods have shown very high levels of accuracy and good agreement in results across platforms. Recently, several commercial platforms with regulatory approval have been developed including Osmetech eSensor, Nanosphere, Infiniti and ParagonDx. ![]() Ī range of genotyping assays for SNPs in CYP2C9 and VKORC1 genes relevant to coumarin anticoagulants have been used previously, including PCR-restriction fragment length polymorphism (RFLP) analysis, pyrosequencing, , Invader and several fluorescence based real time PCR methods. In addition to warfarin, EU-PACT is assessing genetic testing in patient groups being prescribed acenocoumarol and phenprocoumon, and is seeking to genotype patients prior to the initiation of treatment. Several clinical trials are currently in progress, including the European EU-PACT which is aiming to recruit almost 3000 patients. It has been estimated that to detect a 10% improvement in time within range for the target international normalised ratio (INR) as a result of including genotyping during initial warfarin dosing, it would be necessary to study 442 cases and 442 controls The only study completed up to the present with numbers of cases in excess of these estimates found that more frequent monitoring of patients based on genotype led to a significant decrease in hospitalisation rates but in that study, genotyping results to enable decisions about clinical management were available only 11 to 60 days (median 32 days) after the start of treatment. These studies have generally not involved determination of a patient's genotype prior to start of treatment, ,, ,, with the exception of one recent study involving 230 patients. Until now, published results from clinical trials involving genotyping have related to warfarin only, and have mainly involved small numbers of patients they are therefore underpowered to identify significant differences in outcomes between cases and controls. This has prompted clinical trials to demonstrate the utility of pharmacogenetic testing in coumarin anticoagulant prescription. In 2007, the US Food and Drug Administration (FDA) Center for Drug Evaluation and Research updated the label of warfarin to include information on genetic testing. It is estimated that these single nucleotide polymorphisms (SNPs) account for about 40% of the variability in response to coumarin dosing regimes, with patient age and height or weight contributing an additional 15%,. Several polymorphisms in the genes encoding the cytochrome P450 2C9 ( CYP2C9) and vitamin K epoxide reductase ( VKORC1) contribute to this variability. It is also now very well established that genetic factors play a role in the variability of a patient's response. Factors such as height, weight and concurrent medications all affect dose requirement. Prescribing these coumarin based derivatives is difficult due to their narrow therapeutic range with patients at risk of haemorrhage if given too high a dose. Oral anticoagulants such as warfarin, acenocoumarol and phenprocoumon are prescribed widely for the treatment of thromboembolic disorders. ![]()
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