title: CYP4F2 1347 G > A & GGCX 12970 C > G polymorphisms: frequency in north Indians & their effect on dosing of acenocoumarol oral anticoagulant.
abstract: OBJECTIVE
  CYP4F2 and γ-glutamyl carboxylase (GGCX) have small but significant roles in the maintenance dose of coumarinic oral anticoagulants (COAs). CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms have been used in the pharmacogenetic dosing algorithms of warfarin for Caucasians and Chinese populations. India has a large population with multiple ethnic groups but there are no reports about the frequencies of these polymorphisms in north Indians. In the present study, we aimed to find out the allelic frequencies of CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms in a north Indian population and relate these to daily maintenance drug dose requirements of COA.
  
  
  METHODS
  CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms were genotyped by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) protocols and Taqman SNP discrimination assays in healthy volunteers (n=102) and patients (n=225) receiving acenocoumarol, an oral anticoagulant, after cardiac valve replacement surgery.
  
  
  RESULTS
  In healthy volunteers, the allele frequencies for CYP4F2 1347 G > A and GGCX 12970 C > G were 43.14 and 1.43 per cent, respectively. No significant differences in mean weight normalized doses of acenocoumarol were found for these CYP4F2 and GGCX genotypes. Binary logistic regression analysis revealed no significant association of any of the genotypes or alleles with the dosing phenotypes for both the SNPs.
  
  
  CONCLUSIONS
  We report distinct frequencies of CYP4F2 1347 G > A and GGCX 12970 C > G polymorphisms in north Indians but these polymorphisms did not have significant bearing on maintenance dose of acenocoumarol oral anticoagulant in cardiac valve replacement patients.
authors.forename: Saurabh Singh
authors.initials: SS
authors.lastname: Rathore
authors.forename: Surendra Kumar
authors.initials: SK
authors.lastname: Agarwal
authors.forename: Shantanu
authors.initials: S
authors.lastname: Pande
authors.forename: Sushil Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Tulika
authors.initials: T
authors.lastname: Mittal
authors.affiliation: Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage*; D000925:Anticoagulants / Q000008:administration & dosage*; D054316:Biomarkers, Pharmacological; D019735:Carbon-Carbon Ligases / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D005787:Gene Frequency; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D007194:India; D016015:Logistic Models; D010597:Pharmacogenetics / Q000379:methods; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D000925:Anticoagulants; D054316:Biomarkers, Pharmacological; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase; D000074:Acenocoumarol