title: VKORC1 pharmacogenetics and pharmacoproteomics in patients on warfarin anticoagulant therapy: transthyretin precursor as a potential biomarker.
abstract: BACKGROUND
  Recognizing specific protein changes in response to drug administration in humans has the potential for the development of personalized medicine. Such changes can be identified by pharmacoproteomics approach based on proteomic technologies. It can also be helpful in matching a particular target-based therapy to a particular marker in a subgroup of patients, in addition to the profile of genetic polymorphism. Warfarin is a commonly prescribed oral anticoagulant in patients with prosthetic valve disease, venous thromboembolism and stroke.
  
  
  RESULTS
  We used a combined pharmacogenetics and iTRAQ-coupled LC-MS/MS pharmacoproteomics approach to analyze plasma protein profiles of 53 patients, and identified significantly upregulated level of transthyretin precursor in patients receiving low dose of warfarin but not in those on high dose of warfarin. In addition, real-time RT-PCR, western blotting, human IL-6 ELISA assay were done for the results validation.
  
  
  CONCLUSIONS
  This combined pharmacogenomics and pharmacoproteomics approach may be applied for other target-based therapies, in matching a particular marker in a subgroup of patients, in addition to the profile of genetic polymorphism.
authors.affiliation: Laboratory of Clinical Pharmacology, Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore, Singapore.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Saminathan
authors.forename: Jing
authors.initials: J
authors.lastname: Bai
authors.forename: Laleh
authors.initials: L
authors.lastname: Sadrolodabaee
authors.forename: Govindasamy Muralidharan
authors.initials: GM
authors.lastname: Karthik
authors.forename: Onkar
authors.initials: O
authors.lastname: Singh
authors.forename: Koilan
authors.initials: K
authors.lastname: Subramaniyan
authors.forename: Chi Bun
authors.initials: CB
authors.lastname: Ching
authors.forename: Wei Ning
authors.initials: WN
authors.lastname: Chen
authors.forename: Balram
authors.initials: B
authors.lastname: Chowbay
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D011228:Prealbumin / Q000096:biosynthesis*; D040901:Proteomics / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry / Q000379:methods; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D015850:Interleukin-6; D011228:Prealbumin; D014859:Warfarin; D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases