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VKORC1 Pharmacogenetics and Pharmacoproteomics in Patients on Warfarin Anticoagulant Therapy: Transthyretin Precursor as a Potential Biomarker

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...

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Autores principales: Saminathan, Ramasamy, Bai, Jing, Sadrolodabaee, Laleh, Karthik, Govindasamy Muralidharan, Singh, Onkar, Subramaniyan, Koilan, Ching, Chi Bun, Chen, Wei Ning, Chowbay, Balram
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001467/
https://www.ncbi.nlm.nih.gov/pubmed/21179214
http://dx.doi.org/10.1371/journal.pone.0015064
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author Saminathan, Ramasamy
Bai, Jing
Sadrolodabaee, Laleh
Karthik, Govindasamy Muralidharan
Singh, Onkar
Subramaniyan, Koilan
Ching, Chi Bun
Chen, Wei Ning
Chowbay, Balram
author_facet Saminathan, Ramasamy
Bai, Jing
Sadrolodabaee, Laleh
Karthik, Govindasamy Muralidharan
Singh, Onkar
Subramaniyan, Koilan
Ching, Chi Bun
Chen, Wei Ning
Chowbay, Balram
author_sort Saminathan, Ramasamy
collection PubMed
description 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.
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spelling pubmed-30014672010-12-21 VKORC1 Pharmacogenetics and Pharmacoproteomics in Patients on Warfarin Anticoagulant Therapy: Transthyretin Precursor as a Potential Biomarker Saminathan, Ramasamy Bai, Jing Sadrolodabaee, Laleh Karthik, Govindasamy Muralidharan Singh, Onkar Subramaniyan, Koilan Ching, Chi Bun Chen, Wei Ning Chowbay, Balram PLoS One Research Article 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. Public Library of Science 2010-12-13 /pmc/articles/PMC3001467/ /pubmed/21179214 http://dx.doi.org/10.1371/journal.pone.0015064 Text en Saminathan et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Saminathan, Ramasamy
Bai, Jing
Sadrolodabaee, Laleh
Karthik, Govindasamy Muralidharan
Singh, Onkar
Subramaniyan, Koilan
Ching, Chi Bun
Chen, Wei Ning
Chowbay, Balram
VKORC1 Pharmacogenetics and Pharmacoproteomics in Patients on Warfarin Anticoagulant Therapy: Transthyretin Precursor as a Potential Biomarker
title VKORC1 Pharmacogenetics and Pharmacoproteomics in Patients on Warfarin Anticoagulant Therapy: Transthyretin Precursor as a Potential Biomarker
title_full VKORC1 Pharmacogenetics and Pharmacoproteomics in Patients on Warfarin Anticoagulant Therapy: Transthyretin Precursor as a Potential Biomarker
title_fullStr VKORC1 Pharmacogenetics and Pharmacoproteomics in Patients on Warfarin Anticoagulant Therapy: Transthyretin Precursor as a Potential Biomarker
title_full_unstemmed VKORC1 Pharmacogenetics and Pharmacoproteomics in Patients on Warfarin Anticoagulant Therapy: Transthyretin Precursor as a Potential Biomarker
title_short VKORC1 Pharmacogenetics and Pharmacoproteomics in Patients on Warfarin Anticoagulant Therapy: Transthyretin Precursor as a Potential Biomarker
title_sort vkorc1 pharmacogenetics and pharmacoproteomics in patients on warfarin anticoagulant therapy: transthyretin precursor as a potential biomarker
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001467/
https://www.ncbi.nlm.nih.gov/pubmed/21179214
http://dx.doi.org/10.1371/journal.pone.0015064
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