title: CYP2C9, VKORC1, CYP4F2, ABCB1 and F5 variants: influence on quality of long-term anticoagulation.
abstract: OBJECTIVE
  The study aims to evaluate the impact of genetic, demographic and clinical data on various measures of outcome of anticoagulation quality in patients.
  
  
  METHODS
  The study consisted of 310 patients receiving long-term oral anticoagulation therapy in our hospital. Apart from demographic and clinical variables, 21 SNPs (in 7 genes) were analyzed and compared with the outcomes of anticoagulation therapy. Various outcomes that were measured are; supra therapeutic INRs (INR >3, >6), anticoagulation stabilization, time taken to stabilize and proportion of INRs within (2-3), above (>3) and below (<2) therapeutic range.
  
  
  RESULTS
  Supra therapeutic INRs were influenced by CYP2C9*2, *3, CYP4F2 rs2108622, VKORC1-1639G>A, 1173C>T, rs55894764 along with concomitant drugs, smoking, body weight and height. Persistently fluctuating INRs/absolute instability correlated with VKORC1-1639G>A, gender, height and body mass index. The time taken to stabilize was associated with CYP4F2 rs2108622, CYP2C9*14, smoking, clinical indication and concomitant drugs. The overall distribution of INR was influenced by variants in CYP4F2 rs2108622, CYP2C9*3, rs9332230, VKORC1 1173C>T, -1639G>A, rs55894764, ABCB1 rs2032582, rs1128503, rs1045642 and F5 rs6025, age, smoking and concomitant drugs.
  
  
  CONCLUSIONS
  Knowledge of factors influencing the quality of long term anticoagulation can help clinicians to customize therapy either by dose variation, therapy with alternate choice of drug, concurrent heparin therapy and/or frequent INR monitoring.
authors.affiliation: Krishna Institute of Medical Sciences (KIMS), KIMS Foundation and Research Center (KFRC), Hyderabad, India; Center of Medical Genetics, Sir Ganga Ram Hospital,, New Delhi; Amity Institute of Biotechnology, Amity University, Noida, India. Electronic address: rishanahar@gmail.com.
authors.forename: Risha
authors.initials: R
authors.lastname: Nahar
authors.affiliation: Center of Medical Genetics, Sir Ganga Ram Hospital,, New Delhi; Department of Neurology, Sir Ganga Ram Hospital, New Delhi, India.
authors.forename: Renu
authors.initials: R
authors.lastname: Saxena
authors.affiliation: Amity Institute of Biotechnology, Amity University, Noida, India; Department of Neurology, Sir Ganga Ram Hospital, New Delhi, India.
authors.forename: Roumi
authors.initials: R
authors.lastname: Deb
authors.affiliation: Division of Peripheral Vascular & Endovascular Sciences, Medicity Medanta Hospital, New Delhi, India; Department of Neurology, Sir Ganga Ram Hospital, New Delhi, India.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Parakh
authors.affiliation: Department of Cardiac Surgery, Sir Ganga Ram Hospital, New Delhi, India; Department of Neurology, Sir Ganga Ram Hospital, New Delhi, India.
authors.forename: Sujay
authors.initials: S
authors.lastname: Shad
authors.affiliation: Department of Neurology, Sir Ganga Ram Hospital, New Delhi, India.
authors.forename: Prahlad K
authors.initials: PK
authors.lastname: Sethi
authors.affiliation: Department of Research, Sir Ganga Ram Hospital, New Delhi, India; Department of Neurology, Sir Ganga Ram Hospital, New Delhi, India.
authors.forename: Parul
authors.initials: P
authors.lastname: Takkar
authors.affiliation: Center of Medical Genetics, Sir Ganga Ram Hospital,, New Delhi.
authors.forename: Ishwar C
authors.initials: IC
authors.lastname: Verma
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D005165:Factor V / Q000235:genetics*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000925:Anticoagulants; C095381:factor V Leiden; D005165:Factor V; 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
keywords: Acenocoumarol; Anticoagulation; Genetic; India; Warfarin