TY - JOUR
T1 - VKORC1 pharmacogenetics and pharmacoproteomics in patients on warfarin anticoagulant therapy
T2 - Transthyretin precursor as a potential biomarker
AU - Saminathan, Ramasamy
AU - Bai, Jing
AU - Sadrolodabaee, Laleh
AU - Karthik, Govindasamy Muralidharan
AU - Singh, Onkar
AU - Subramaniyan, Koilan
AU - Ching, Chi Bun
AU - Chen, Wei Ning
AU - Chowbay, Balram
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78650781729&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78650781729&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0015064
DO - 10.1371/journal.pone.0015064
M3 - Article
C2 - 21179214
AN - SCOPUS:78650781729
SN - 1932-6203
VL - 5
JO - PLoS One
JF - PLoS One
IS - 12
M1 - e15064
ER -
