Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin

What is known and Objectives: Testing for cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) variant alleles is recommended by the FDA for dosing of warfarin. However, dose prediction models derived from data obtained in one population may not be applicable to a...

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Main Authors:	Teh, L. K., Langmia, I. M., M. H., Fazleen Haslinda, Ngow, Harris Abdullah, Roziah, M. J., Harun, R., Zakaria, Z. A., Salleh, M. Z.
Format:	Article
Language:	English
Published:	Blackwell Publishing 2011
Subjects:	QP Physiology RC Internal medicine RM Therapeutics. Pharmacology
Online Access:	http://irep.iium.edu.my/5105/ http://irep.iium.edu.my/5105/ http://irep.iium.edu.my/5105/2/Cyp2c9_and_VKROC.pdf

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recordtype	eprints
spelling	iium-51052011-10-28T04:21:49Z http://irep.iium.edu.my/5105/ Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C93 among patients on warfarin Teh, L. K. Langmia, I. M. M. H., Fazleen Haslinda Ngow, Harris Abdullah Roziah, M. J. Harun, R. Zakaria, Z. A. Salleh, M. Z. QP Physiology RC Internal medicine RM Therapeutics. Pharmacology What is known and Objectives: Testing for cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) variant alleles is recommended by the FDA for dosing of warfarin. However, dose prediction models derived from data obtained in one population may not be applicable to another. We therefore studied the impact of genetic polymorphisms of CYP2C9 and VKORC1 on warfarin dose requirement in Malaysia. Methods: Patients who were attending clinics at our hospital and prescribed warfarin with stabilized INR levels of 2-4 were selected. DNA was extracted from blood samples and subsequently genotyped for CYP2C91, 2, 3, VKORC1 (G-1639A) and VKORC1 C1173T. Linear regression modelling using age, CYP2C9 and VKORC1 genotypes, sex, weight and height was undertaken to define a warfarin dosing algorithm. An initial model was developed using data from one cohort of patients and validated using data from a second cohort. Results and Discussion: A model which included age and variants of CYP2C9 and VKORC1 account for about 37% of the variability in warfarin dose required to achieve INR of 2-4. Among the parameters evaluated, only VKORC1 (G-1639A) and (C1173T) alleles, and age correlated with warfarin dose at 6 month. The mean dose predicted using the algorithm derived from cohort 1 was lower than the actual dose for cohort 2 (3·30 mg, SD 0·84 vs. 3·45 mg, SD 1·42). There was no relationship between INR values and the dose taken by the patients. Race, sex, weight and height did not correlate with dose. What is new and Conclusion: This study identifies factors which affect warfarin dosing in the Malaysia population. However, our best model does not account sufficiently for the variability in dose requirements for it to be used in dose prediction for the individual patient. Other important influential factors affecting warfarin dose requirement remain to be identified. Blackwell Publishing 2011 Article PeerReviewed application/pdf en http://irep.iium.edu.my/5105/2/Cyp2c9_and_VKROC.pdf Teh, L. K. and Langmia, I. M. and M. H., Fazleen Haslinda and Ngow, Harris Abdullah and Roziah, M. J. and Harun, R. and Zakaria, Z. A. and Salleh, M. Z. (2011) Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin. Journal of clinical pharmacy and therapeutics. ISSN 1365-2710 DOI: 10.1111/j.1365-2710.2011.01262.x.
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	QP Physiology RC Internal medicine RM Therapeutics. Pharmacology
spellingShingle	QP Physiology RC Internal medicine RM Therapeutics. Pharmacology Teh, L. K. Langmia, I. M. M. H., Fazleen Haslinda Ngow, Harris Abdullah Roziah, M. J. Harun, R. Zakaria, Z. A. Salleh, M. Z. Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin
description	What is known and Objectives: Testing for cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) variant alleles is recommended by the FDA for dosing of warfarin. However, dose prediction models derived from data obtained in one population may not be applicable to another. We therefore studied the impact of genetic polymorphisms of CYP2C9 and VKORC1 on warfarin dose requirement in Malaysia. Methods: Patients who were attending clinics at our hospital and prescribed warfarin with stabilized INR levels of 2-4 were selected. DNA was extracted from blood samples and subsequently genotyped for CYP2C91, 2, *3, VKORC1 (G-1639A) and VKORC1 C1173T. Linear regression modelling using age, CYP2C9 and VKORC1 genotypes, sex, weight and height was undertaken to define a warfarin dosing algorithm. An initial model was developed using data from one cohort of patients and validated using data from a second cohort. Results and Discussion: A model which included age and variants of CYP2C9 and VKORC1 account for about 37% of the variability in warfarin dose required to achieve INR of 2-4. Among the parameters evaluated, only VKORC1 (G-1639A) and (C1173T) alleles, and age correlated with warfarin dose at 6 month. The mean dose predicted using the algorithm derived from cohort 1 was lower than the actual dose for cohort 2 (3·30 mg, SD 0·84 vs. 3·45 mg, SD 1·42). There was no relationship between INR values and the dose taken by the patients. Race, sex, weight and height did not correlate with dose. What is new and Conclusion: This study identifies factors which affect warfarin dosing in the Malaysia population. However, our best model does not account sufficiently for the variability in dose requirements for it to be used in dose prediction for the individual patient. Other important influential factors affecting warfarin dose requirement remain to be identified.
format	Article
author	Teh, L. K. Langmia, I. M. M. H., Fazleen Haslinda Ngow, Harris Abdullah Roziah, M. J. Harun, R. Zakaria, Z. A. Salleh, M. Z.
author_facet	Teh, L. K. Langmia, I. M. M. H., Fazleen Haslinda Ngow, Harris Abdullah Roziah, M. J. Harun, R. Zakaria, Z. A. Salleh, M. Z.
author_sort	Teh, L. K.
title	Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin
title_short	Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin
title_full	Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin
title_fullStr	Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin
title_full_unstemmed	Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin
title_sort	clinical relevance of vkorc1 (g-1639a and c1173t) and cyp2c9*3 among patients on warfarin
publisher	Blackwell Publishing
publishDate	2011
url	http://irep.iium.edu.my/5105/ http://irep.iium.edu.my/5105/ http://irep.iium.edu.my/5105/2/Cyp2c9_and_VKROC.pdf
first_indexed	2023-09-18T20:13:35Z
last_indexed	2023-09-18T20:13:35Z
_version_	1777407639247912960

Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin

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