The impact of R353Q genetic polymorphism in coagulation factor VII on the initial anticoagulant effect exerted by warfarin.
Eur J Clin Pharmacol
; 75(3): 343-350, 2019 Mar.
Article
en En
| MEDLINE
| ID: mdl-30411147
ABSTRACT
BACKGROUND:
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).OBJECTIVE:
Evaluate the role of R353Q in the initial response to warfarin.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Warfarina
/
Coagulación Sanguínea
/
Factor VII
/
Polimorfismo de Nucleótido Simple
/
Anticoagulantes
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Eur J Clin Pharmacol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Israel