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




VKORC1 Pharmacogenetics and Pharmacoproteomics in Patients on Warfarin Anticoagulant Therapy: Transthyretin Precursor as a Potential Biomarker - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Ramasamy Saminathan , Jing Bai , Laleh Sadrolodabaee , Govindasamy Muralidharan Karthik, Onkar Singh, Koilan Subramaniyan, Chi Bu

Fuente: http://plos.srce.hr/



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