Identification of biomarker in patients on high dose warfarin : an iTRAQ-coupled LC-MS/MS approach

• Main Author: Lee, Joanne Hui Yi.
• Other Authors: Chen Wei Ning, William
• Format: Final Year Project
• Language: English
• Published: 2009
• Subjects: DRNTU::Engineering::Chemical engineering::Biotechnology
• Online Access: http://hdl.handle.net/10356/16452
• Institution: Nanyang Technological University

Warfarin is a widely prescribed anticoagulant for the treatment and prevention of thrombotic diseases. Warfarin has a narrow therapeutic range and a given dose has more than 10-fold inter-individual variability in its pharmacodynamic effects. An insufficient dose may fail to prevent thromboembolism while an overdose increases the risk of bleeding. [4] Thus Warfarin therapy management is particularly challenging because of the difficulties inherent in achieving and maintaining the international therapeutic range (INR) in the therapeutic range required for anticoagulation. Current medical advancements have improved the dosing of Warfarin therapy through the use of genomic biomarkers where the metabolisms of Warfarin in relation to various patients are being studied. Both the CYP2C9 and VKORC1 gene have been approved by the FDA to be used when putting patients on Warfarin therapy. However genomic biomarkers are very often not as accurate as proteomic biomarkers and it is always expressed in forms of percentage inference. Since the human plasma consist of very broad dynamic range of protein relative abundances, it is believed that many important proteins such as biomarkers might have escaped detection due to past technologies. Coupled with the use of LC/MS-MS Machine, we manage to find 2 potential proteomic biomarkers in the plasma of patients undergoing Warfarin therapy namely 1) Unk1 Protein - Homo sapiens (Human) and 2) Apolipoprotein A-I precursor (Apo-AI) (ApoA-I) [Contains: Apolipoprotein A-I(1-242)] - Homo sapiens (Human).