title: Frequency of CYP2C9 polymorphisms affecting warfarin metabolism in a large anticoagulant clinic cohort.
abstract: OBJECTIVE
  To assess allele frequency and genotype distribution of CYP2C9 polymorphisms in patients (n = 189) attending an anticoagulant clinic in comparison to control patients (n = 177) and also to assess if the patients with variant genotypes require lower doses of warfarin.
  
  
  METHODS
  Genotyping of the common CYP2C9 variants *2 and *3 was carried out by multiplexed PCR-RFLP while the *5 and *6 allele variants were genotyped by singleton PCR-RFLP. DNA sequencing was used to confirm genotype in all specimens with *3, *4 and *6 alleles.
  
  
  RESULTS
  CYP2C9 allele frequencies in patients were 0.81 for *1, 0.11 for *2 and 0.08 for *3, compared to 0.88, 0.08 and 0.04, respectively, in controls. Patients with *1/*3 and *X/*X (where *X is *2 or *3) genotypes required 32 to 67% less warfarin in comparison to patients with the normal *1/*1 genotype. Other alleles were observed in less than 1% of subjects.
  
  
  CONCLUSIONS
  Allele frequencies and genotypes for CYP2C9*2 and *3 variants in patients on warfarin are not statistically different from controls whether or not they are stratified for ethnicity. Less common genotypes (*4, *5, *6) do not contribute significantly to warfarin sensitivity among patients attending a routine anticoagulation clinic. CYP2C9 genotype predicts warfarin dosage even in an uncontrolled, retrospective survey of unselected patients on warfarin therapy.
authors.affiliation: School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
authors.forename: Majid
authors.initials: M
authors.lastname: Moridani
authors.forename: Lei
authors.initials: L
authors.lastname: Fu
authors.forename: Rita
authors.initials: R
authors.lastname: Selby
authors.forename: Francisco
authors.initials: F
authors.lastname: Yun
authors.forename: Tatjana
authors.initials: T
authors.lastname: Sukovic
authors.forename: Betty
authors.initials: B
authors.lastname: Wong
authors.forename: David E C
authors.initials: DE
authors.lastname: Cole
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001483:Base Sequence; D015331:Cohort Studies; D065729:Cytochrome P-450 CYP2C9; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D013927:Thrombosis / Q000517:prevention & control; D014859:Warfarin / Q000493:pharmacokinetics*
chemical_list: D000925:Anticoagulants; D017931:DNA Primers; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases