Estimation of the warfarin dose with clinical and pharmacogenetic data

摘要: Warfarin is one of the most widely used anticoagulants in world. Treatment complicated by a large inter-individual variation dose needed to reach adequate levels anticoagulation i.e. INR 2.0 – 3.0. The objective this thesis was evaluate which factors, mainly genetic but also non-genetic, that affect response warfarin terms required maintenance dose, efficacy and safety with special focus on prediction.Through candidate gene genome-wide studies, we have shown genes CYP2C9 VKORC1 are major determinants dose. By combining SNPs *2, *3 rs9923231 clinical factors age, height, weight, ethnicity, amiodarone use inducers (carbamazepine, phenytoin or rifampicin) into prediction model (the IWPC model) can explain 43 % 51 Patients requiring doses < 29 mg/week ≥ 49 benefitted from pharmacogenetic dosing. Further, difference across ethnicities percent variance explained largely accounted for allele frequency rs9923231. Other novel affecting (NEDD4 DDHD1), as well replicated CYP4F2 gene, small effects predictions not likely be cost-effective, unless inexpensive genotyping available.Three types models dosing exist: models, loading revision models. combination these three currently being treatment arm European Pharmacogenetics Anticoagulant Therapy (EU-PACT) study. trials aiming prove validity utility underway.The future relies results ongoing availability cost-effectiveness driven compared new oral anticoagulant drugs.