title: Effect of VKORC1, CYP2C9 and CYP4F2 genetic variants in early outcomes during acenocoumarol treatment.
abstract: OBJECTIVE
  To analyze VKORC1, CYP2C9 and CYP4F2 polymorphisms in relation to the main outcomes in the first stages of acenocoumarol therapy.
  
  
  METHODS
  Nine hundred and forty one patients who had started therapy and in whom time to stable dosage, time to over-anticoagulation and adverse events occurred during 3 first months were retrospectively analyzed.
  
  
  RESULTS
  VKORC1 AA patients needed fewer days to reach stable dosage (p = 0.017). International normalized ratio [INR] at 72 h, and VKORC1 and CYP2C9 genotypes conditioned INR values >2.5 (p < 0.001, p = 0.002 and p < 0.001, respectively), whereas CYP4F2 T carriers had a low risk of the same outcome (p = 0.009). In regards to combined genotypes, CYP4F2 had a significant effect on over-anticoagulation at the beginning of therapy except for the VKORC1 AA and CYP2C9*3 combination.
  
  
  CONCLUSIONS
  In addition to VKORC1 and CYP2C9, CYP4F2 gene has a slight but significant role in reaching INR >2.5 during the first weeks of acenocoumarol therapy.
authors: Hospital Universitario Morales Meseguer & Centro Regional de Hemodonacion, University of Murcia, Ronda de Garay s/n, 30003, IMIB, Murcia, Spain.
authors: Juan Jose
authors: JJ
authors: Cerezo-Manchado
authors: Vanessa
authors: V
authors: Roldan
authors: Mario
authors: M
authors: Rosafalco
authors: Ana Isabel
authors: AI
authors: Anton
authors: Ana Belen
authors: AB
authors: Arroyo
authors: Nuria
authors: N
authors: Garcia-Barbera
authors: Ana Belen
authors: AB
authors: Martínez
authors: Jose
authors: J
authors: Padilla
authors: Javier
authors: J
authors: Corral
authors: Vicente
authors: V
authors: Vicente
authors: Rocio
authors: R
authors: Gonzalez-Conejero
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D054316:Biomarkers, Pharmacological; D001778:Blood Coagulation Disorders / Q000188:drug therapy* / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*
chemical_list: D054316:Biomarkers, Pharmacological; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D000074:Acenocoumarol
keywords: CYP2C9; CYP4F2; VKORC1; acenocoumarol; outcomes; pharmacogenetics; polymorphisms