Pharmacogenetics of VKORC1 in warfarin resistant patients.

Warfarin is a commonly prescribed anticoagulant that displays wide inter-individual variability in treatment response and dosage. It acts by inhibiting the vitamin K epoxide reductase (VKOR) enzyme in the liver. Genetic variations in vitamin K epoxide reductase complex subunit 1(VKORC1), have been a...

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Main Author: Ong, Jacqueline Kai Mei.
Other Authors: Balram Chowbay
Format: Final Year Project (FYP)
Language:English
Published: 2010
Subjects:
Online Access:http://hdl.handle.net/10356/41759
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author Ong, Jacqueline Kai Mei.
author2 Balram Chowbay
author_facet Balram Chowbay
Ong, Jacqueline Kai Mei.
author_sort Ong, Jacqueline Kai Mei.
collection NTU
description Warfarin is a commonly prescribed anticoagulant that displays wide inter-individual variability in treatment response and dosage. It acts by inhibiting the vitamin K epoxide reductase (VKOR) enzyme in the liver. Genetic variations in vitamin K epoxide reductase complex subunit 1(VKORC1), have been associated with differential dose requirement of warfarin. However, high variability in treatment response is still observed. The hypothesis is that other functional polymorphisms in VKORC1 may influence the enzymatic activity of VKOR, leading to variation in the pharmacodynamics of warfarin. Thus, the aim of this study is to investigate novel polymorphisms in VKORC1 that may influence the activity of VKOR in patients receiving varying warfarin dosages. In this study, the VKORC1 gene was screened for novel polymorphisms in 32 subjects. A total of fifteen mutations were found, of which eight were novel. In particular, 337 G>A, 1849_1850 insertion T and 4851 T>G were found to be present in higher frequencies in the high-dose patients. This exploratory study provides the basis for future studies of the pharmacogenetics of VKORC1 in a larger population.
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spelling ntu-10356/417592023-02-28T18:06:44Z Pharmacogenetics of VKORC1 in warfarin resistant patients. Ong, Jacqueline Kai Mei. Balram Chowbay School of Biological Sciences National Cancer Centre Singapore DRNTU::Science::Biological sciences::Microbiology::Drug Resistance Warfarin is a commonly prescribed anticoagulant that displays wide inter-individual variability in treatment response and dosage. It acts by inhibiting the vitamin K epoxide reductase (VKOR) enzyme in the liver. Genetic variations in vitamin K epoxide reductase complex subunit 1(VKORC1), have been associated with differential dose requirement of warfarin. However, high variability in treatment response is still observed. The hypothesis is that other functional polymorphisms in VKORC1 may influence the enzymatic activity of VKOR, leading to variation in the pharmacodynamics of warfarin. Thus, the aim of this study is to investigate novel polymorphisms in VKORC1 that may influence the activity of VKOR in patients receiving varying warfarin dosages. In this study, the VKORC1 gene was screened for novel polymorphisms in 32 subjects. A total of fifteen mutations were found, of which eight were novel. In particular, 337 G>A, 1849_1850 insertion T and 4851 T>G were found to be present in higher frequencies in the high-dose patients. This exploratory study provides the basis for future studies of the pharmacogenetics of VKORC1 in a larger population. Bachelor of Science in Biomedical Sciences 2010-08-11T04:56:25Z 2010-08-11T04:56:25Z 2010 2010 Final Year Project (FYP) http://hdl.handle.net/10356/41759 en Nanyang Technological University 27 p. application/pdf
spellingShingle DRNTU::Science::Biological sciences::Microbiology::Drug Resistance
Ong, Jacqueline Kai Mei.
Pharmacogenetics of VKORC1 in warfarin resistant patients.
title Pharmacogenetics of VKORC1 in warfarin resistant patients.
title_full Pharmacogenetics of VKORC1 in warfarin resistant patients.
title_fullStr Pharmacogenetics of VKORC1 in warfarin resistant patients.
title_full_unstemmed Pharmacogenetics of VKORC1 in warfarin resistant patients.
title_short Pharmacogenetics of VKORC1 in warfarin resistant patients.
title_sort pharmacogenetics of vkorc1 in warfarin resistant patients
topic DRNTU::Science::Biological sciences::Microbiology::Drug Resistance
url http://hdl.handle.net/10356/41759
work_keys_str_mv AT ongjacquelinekaimei pharmacogeneticsofvkorc1inwarfarinresistantpatients