Warfarin anticoagulant therapy: a Southern Italy pharmacogenetics-based dosing model
| Autor: | Alfonso Meccariello, Dino Franco Vitale, Rosario Liguori, Angelo Severini, Cristina Mazzaccara, Vittorio Simeon, Corrado Perricone, Lucia Sacchetti, Valeria Conti, Pasquale Meccariello, Mario Toriello, Amelia Filippelli |
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| Přispěvatelé: | Mazzaccara, Cristina, V., Conti, R., Liguori, V., Simeon, M., Toriello, A., Severini, C., Perricone, A., Meccariello, P., Meccariello, D. F., Vitale, A., Filippelli, Sacchetti, Lucia, Conti, Valeria, Liguori, Rosario, Simeon, Vittorio, Toriello, Mario, Severini, Angelo, Perricone, Corrado, Meccariello, Alfonso, Meccariello, Pasquale, Vitale, Dino Franco, Filippelli, Amelia |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Epidemiology CYP4F2 lcsh:Medicine Pharmacology Cardiovascular Polymerase Chain Reaction Cytochrome P-450 Enzyme System lcsh:Science Chromatography High Pressure Liquid education.field_of_study Multidisciplinary Anticoagulant Genomics Middle Aged Italy Cardiovascular Diseases Medicine Regression Analysis Vitamin K epoxide reductase Female VKORC1 Aryl Hydrocarbon Hydroxylases Algorithms medicine.drug Research Article medicine.medical_specialty Drugs and Devices Genotype medicine.drug_class Population Biology Cardiovascular Pharmacology Drug Administration Schedule Genetic Mutation Internal medicine Vitamin K Epoxide Reductases medicine Genetics Humans Genetic Testing Cytochrome P450 Family 4 International Normalized Ratio education CYP2C9 Alleles Aged Cytochrome P-450 CYP2C9 Evolutionary Biology Dose-Response Relationship Drug Pharmacoepidemiology lcsh:R Warfarin Personalized Medicine Computational Biology Anticoagulants Human Genetics Pharmacogenetics Genetics of Disease Genetic Polymorphism lcsh:Q Pharmacogenomics Population Genetics |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 8, p e71505 (2013) |
| Popis: | Background and Aim: Warfarin is the most frequently prescribed anticoagulant worldwide. However, warfarin therapy is associated with a high risk of bleeding and thromboembolic events because of a large interindividual dose-response variability. We investigated the effect of genetic and non genetic factors on warfarin dosage in a South Italian population in the attempt to setup an algorithm easily applicable in the clinical practice.Materials and Methods: A total of 266 patients from Southern Italy affected by cardiovascular diseases were enrolled and their clinical and anamnestic data recorded. All patients were genotyped for CYP2C9*2,*3, CYP4F2*3, VKORC1-1639 G>A by the TaqMan assay and for variants VKORC1 1173 C>T and VKORC1 3730 G>A by denaturing high performance liquid chromatography and direct sequencing. The effect of genetic and not genetic factors on warfarin dose variability was tested by multiple linear regression analysis, and an algorithm based on our data was established and then validated by the Jackknife procedure.Results: Warfarin dose variability was influenced, in decreasing order, by VKORC1-1639 G>A (29.7%), CYP2C9*3 (11.8%), age (8.5%), CYP2C9*2 (3.5%), gender (2.0%) and lastly CYP4F2*3 (1.7%); VKORC1 1173 C>T and VKORC1 3730 G>A exerted a slight effect ( |
| Databáze: | OpenAIRE |
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