Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0015064
Title: VKORC1 pharmacogenetics and pharmacoproteomics in patients on warfarin anticoagulant therapy: Transthyretin precursor as a potential biomarker
Authors: Saminathan R.
Bai J.
Sadrolodabaee L.
Karthik G.M.
Singh O.
Subramaniyan K.
Ching C.B. 
Chen W.N.
Chowbay B. 
Keywords: biological marker
interleukin 6
multiprotein complex
prealbumin
unclassified drug
vitamin K epoxide reductase complex subunit 1
vitamin K group
warfarin
anticoagulant agent
biological marker
interleukin 6
menadione epoxidase
mixed function oxidase
prealbumin
warfarin
adult
aged
anticoagulant therapy
article
cell strain HepG2
controlled study
drug dose comparison
drug megadose
enzyme linked immunosorbent assay
female
gene expression profiling
genetic polymorphism
human
human cell
liquid chromatography
low drug dose
major clinical study
male
pharmacogenetics
proteomics
real time polymerase chain reaction
reverse transcription polymerase chain reaction
tandem mass spectrometry
upregulation
Western blotting
biosynthesis
cohort analysis
genetics
liver
metabolism
methodology
tumor cell line
Anticoagulants
Biological Markers
Cell Line, Tumor
Cohort Studies
Enzyme-Linked Immunosorbent Assay
Humans
Interleukin-6
Liver
Mixed Function Oxygenases
Pharmacogenetics
Polymorphism, Genetic
Prealbumin
Proteomics
Reverse Transcriptase Polymerase Chain Reaction
Tandem Mass Spectrometry
Warfarin
Issue Date: 2010
Citation: Saminathan R., Bai J., Sadrolodabaee L., Karthik G.M., Singh O., Subramaniyan K., Ching C.B., Chen W.N., Chowbay B. (2010). VKORC1 pharmacogenetics and pharmacoproteomics in patients on warfarin anticoagulant therapy: Transthyretin precursor as a potential biomarker. PLoS ONE 5 (12) : e15064. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0015064
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. Methods and Finding: 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. Conclusion: 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. © 2010 Saminathan et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161800
ISSN: 19326203
DOI: 10.1371/journal.pone.0015064
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