The impact of R353Q genetic polymorphism in coagulation factor VII on the initial anticoagulant effect exerted by warfarin
| Autor: | Chanan Shaul, Liat Deutsch, Yoseph Caraco, Gilad Rosenberg, Simcha Blotnick |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male medicine.medical_specialty Anticoagulant effect Genotype Glutamine Arginine Polymorphism Single Nucleotide 030226 pharmacology & pharmacy Gastroenterology Young Adult 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Vitamin K Epoxide Reductases Internal medicine medicine Humans heterocyclic compounds Pharmacology (medical) International Normalized Ratio cardiovascular diseases 030212 general & internal medicine Blood Coagulation CYP2C9 Coagulation factor VII Cytochrome P-450 CYP2C9 Pharmacology Cholesterol business.industry Genetic variants Warfarin Anticoagulants General Medicine Factor VII chemistry Multivariate Analysis Linear Models VKORC1 Drug Monitoring business medicine.drug |
| Zdroj: | European Journal of Clinical Pharmacology. 75:343-350 |
| ISSN: | 1432-1041 0031-6970 |
| DOI: | 10.1007/s00228-018-2594-2 |
| Popis: | The initial rise in INR following warfarin is attributed to rapid decline in coagulation factor VII (F7). The R353Q polymorphism in F7 accounts for approximately 1/3 of the variability in F7 activity (FVIIc). Evaluate the role of R353Q in the initial response to warfarin. Twenty-eight healthy, males, carrying CYP2C9*1/*1 (n = 14), CYP2C9*1/*2 (n = 4) or CYP2C9*1/*3 (n = 10) genotypes, received single 20 mg warfarin. S&R-warfarin concentrations, INR, and FVIIc were monitored periodically for 7 days. Baseline and maximal INR were 5.6% and 33.5% higher among carriers of the RQ (n = 12) as compared with those carrying the RR (n = 16) genotype (p = 0.032, p = 0.003, respectively). Baseline and nadir FVIIc were 21.6% and 42.0% lower among subjects carrying the RQ as compared with carriers of the RR genotype (p = 0.001, p = 0.007 respectively). In multiple regression analysis, R353Q predicted 36.6% of the variability in peak INR whereas 20.2%, 9.9%, and 5.9% were attributed to VKORC1 genetic polymorphism, cholesterol concentration, and S Warfarin concentration after 24 h, respectively. R353Q genetic polymorphism plays a key role in determining the initial response to warfarin. The incorporation of this genetic variant into warfarin loading algorithm should be further investigated. |
| Databáze: | OpenAIRE |
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