title: Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and their influence on warfarin maintenance dose: proposal for a new dosing regimen.
abstract: BACKGROUND
  Warfarin is one of the most widely used anticoagulants, yet interindividual differences in drug response, a narrow therapeutic range and a high risk of bleeding or stroke complicate its use. We aimed to determine the allele and genotype frequency of VKORC1 1173 C>T, CYP2C9*2 and CYP2C9*3 variant polymorphisms in the Egyptian population and to evaluate their influence on the interindividual differences in warfarin dosage.
  
  
  METHODS
  A total of 154 unrelated healthy adult patients and 46 warfarin-treated patients were included. SYBR Green-based real-time polymerase chain reaction (PCR) assay was used for studying VKORC1 (C1173T) and CYP2C9*3 polymorphisms. Mutagenically separated PCR assay was used to detect the CYP2C9*2 allele.
  
  
  RESULTS
  VKORC1 genotype frequencies were 11%, 24% and 65% for CC, CT and TT, respectively. The prevalence of CYP2C9 haplotypes was 81% (*1\*1), 3.3% (*1\*2), 9.7% (*1\*3), 4.5% (*2\*2) and 0.65% (2\*3 and *3\*3). VKORC1 TT and CYP2C9*2\*2 were associated with a significantly lower warfarin dose. VKORC1 and CYP2C9 accounted for 31.7% and 15.6% of warfarin dose variability, respectively, and together with clinical factors explained 61.3% of total variability.
  
  
  CONCLUSIONS
  VKORC1-TT and CYP2C9 *1/*1 are the most prevalent genotypes among Egyptians. Patients with VKORC1-TT genotype required a lower warfarin dose.
authors.affiliation: Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: M S
authors.initials: MS
authors.lastname: El Din
authors.forename: D G
authors.initials: DG
authors.lastname: Amin
authors.forename: S B
authors.initials: SB
authors.lastname: Ragab
authors.forename: E E
authors.initials: EE
authors.lastname: Ashour
authors.forename: M H
authors.initials: MH
authors.lastname: Mohamed
authors.forename: A M
authors.initials: AM
authors.lastname: Mohamed
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D004534:Egypt; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases