title: Effect of CYP2C9 and VKORC1 genetic variations on warfarin dose requirements in Indian patients.
abstract: BACKGROUND
  Warfarin, an oral anticoagulant is used in patients who are at increased risk of developing blood clots. The management of warfarin therapy is challenging because it shows large inter and intra individual variability in patient response due to factors like age, gender, diet, concurrent drug interactions and variations in CYP2C9 and VKORC1 genes. Studies implicate that polymorphisms in VKORC1 and CYP2C9 genes are associated with reduced doses of warfarin. The aim of our current study was to characterize the effects of VKORC1 and CYP2C9 gene variations that contribute to variability in warfarin dosing in Indian patients.
  
  
  METHODS
  Genomic DNA was extracted from 103 patients undergoing warfarin therapy. Their mean daily warfarin dose, INR and demographics were recorded and genotyping of VKORC1 and CYP2C9 gene was performed by PCR-RFLP method.
  
  
  RESULTS
  Individuals with wild type genotypes required highest mean warfarin dosage of 4.72 mg/day while VKORC1 variants required 3.6 mg/day to maintain their therapeutic INR. CYP2C9*2 genotype was not found to affect the warfarin maintenance dosages. The odds ratio for developing supra therapeutic INR in patients carrying VKORC1 variant allele when compared to wild types was 13.96 (95% CI; 4.85 - 44.65. Other factors affecting warfarin dosages were age and weight.
  
  
  CONCLUSIONS
  Inclusion of pharmacogenetic data along with clinical parameters would help better predict warfarin doses in Indian patients.
authors.affiliation: Research Laboratories, P.D. Hinduja National Hospital and Medical Research Centre, V. S. Marg, Mahim, Mumbai-400016, India. dr_tashavaid@hindujahospital.com or tashavaid@gmail.co.
authors.forename: Sripriya
authors.initials: S
authors.lastname: Natarajan
authors.forename: Chandrashekhar K
authors.initials: CK
authors.lastname: Ponde
authors.forename: Rajesh M
authors.initials: RM
authors.lastname: Rajani
authors.forename: Farah
authors.initials: F
authors.lastname: Jijina
authors.forename: Roopkumar
authors.initials: R
authors.lastname: Gursahani
authors.forename: Pradnya P
authors.initials: PP
authors.lastname: Dhairyawan
authors.forename: Tester F
authors.initials: TF
authors.lastname: Ashavaid
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects* / Q000235:genetics*; D016009:Chi-Square Distribution; D065729:Cytochrome P-450 CYP2C9; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D019934:International Normalized Ratio; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D064417:Vitamin K Epoxide Reductases / Q000235:genetics* / Q000378:metabolism; D014859:Warfarin / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases