VKORC1 Haplotypes in patients treated with warfarin

Background: Warfarin has very narrow therapeutic windows and large individual variability. Genetic variants encoding VKORC1 gene has resulted in altered sensitivity to warfarin or warfarin resistance. Nine haplotypes (H1-H9) of VKORC1 had been categorized with reference to 10 SNPs (Gen Bank accessio...

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Main Authors:	Beshna, E, Teh , Lay Kek, Ngow, Harris Abdullah, Harun, Roslan, Salleh, Mohd Zaki
Format:	Conference or Workshop Item
Language:	English
Published:	2010
Subjects:	RC Internal medicine RM Therapeutics. Pharmacology
Online Access:	http://irep.iium.edu.my/5241/ http://irep.iium.edu.my/5241/1/Pharmacogenomic_VKROC1_Halotype_Abstract_Poster.pdf

id	iium-5241
recordtype	eprints
spelling	iium-52412011-11-16T14:27:14Z http://irep.iium.edu.my/5241/ VKORC1 Haplotypes in patients treated with warfarin Beshna, E Teh , Lay Kek Ngow, Harris Abdullah Harun, Roslan Salleh, Mohd Zaki RC Internal medicine RM Therapeutics. Pharmacology Background: Warfarin has very narrow therapeutic windows and large individual variability. Genetic variants encoding VKORC1 gene has resulted in altered sensitivity to warfarin or warfarin resistance. Nine haplotypes (H1-H9) of VKORC1 had been categorized with reference to 10 SNPs (Gen Bank accession number AY587020). Objective: To determine the haplotypes frequencies of VKORC1 gene among the patients prescribed warfarin and to correlate the dose, INR and bleeding with haplotypes. Method: A total of 158 patients prescribed warfarin and met the inclusion criteria were recruited after informed consent. Five ml of blood was drawn from each patient and DNA was extracted for genotyping of VKORC1 variants. Two steps PCR methods were developed to identify all the 10 SNPs. The optimized method was validated by direct sequencing. Result: Twenty-six (26) haplotypes were inferred from 10 common SNPs. Only four haplotypes have frequency more than 2.5%. The VKORC1 haplotypes with the highest frequency was H1 (72.5%) followed by H6 (3.8%), H7 (7.3%) and H10 (2.5%). Two haplotypes (H1 and H10) were associated with a low warfarin dose requirement (2.9 and 2.63 mg per day; p<0.01)) while H6 and H7 were associated with high dose requirement (4.55 and 4.83 mg per day; p<0.01). The average INR was approximately 2.4 and did not differ significantly among the patients classified according to VKORC1 haplotype combination (P value=0.196). The multiple regression analysis (Enter method) indicated that VKORC1 accounted for 24.8 % the variation in warfarin dose. Conclusion: VKORC1 haplotype provided a good correlation for different warfarin dose requirements. Genotyping of patients before warfarin is thus useful to predict more accurately dose required. Corresponding author: M. Z. Salleh, Head, Pharmacogenomics Centre, Faculty of Pharmacy, Universiti Teknologi MARA Malaysia. Acknowledgement: This study was supported by kecermerlangan’s UiTM. 2010 Conference or Workshop Item NonPeerReviewed application/pdf en http://irep.iium.edu.my/5241/1/Pharmacogenomic_VKROC1_Halotype_Abstract_Poster.pdf Beshna, E and Teh , Lay Kek and Ngow, Harris Abdullah and Harun, Roslan and Salleh, Mohd Zaki (2010) VKORC1 Haplotypes in patients treated with warfarin. In: National Biotechonology Seminar , 24th-26th May 2010, Putra World Trade Center.
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	RC Internal medicine RM Therapeutics. Pharmacology
spellingShingle	RC Internal medicine RM Therapeutics. Pharmacology Beshna, E Teh , Lay Kek Ngow, Harris Abdullah Harun, Roslan Salleh, Mohd Zaki VKORC1 Haplotypes in patients treated with warfarin
description	Background: Warfarin has very narrow therapeutic windows and large individual variability. Genetic variants encoding VKORC1 gene has resulted in altered sensitivity to warfarin or warfarin resistance. Nine haplotypes (H1-H9) of VKORC1 had been categorized with reference to 10 SNPs (Gen Bank accession number AY587020). Objective: To determine the haplotypes frequencies of VKORC1 gene among the patients prescribed warfarin and to correlate the dose, INR and bleeding with haplotypes. Method: A total of 158 patients prescribed warfarin and met the inclusion criteria were recruited after informed consent. Five ml of blood was drawn from each patient and DNA was extracted for genotyping of VKORC1 variants. Two steps PCR methods were developed to identify all the 10 SNPs. The optimized method was validated by direct sequencing. Result: Twenty-six (26) haplotypes were inferred from 10 common SNPs. Only four haplotypes have frequency more than 2.5%. The VKORC1 haplotypes with the highest frequency was H1 (72.5%) followed by H6 (3.8%), H7 (7.3%) and H10 (2.5%). Two haplotypes (H1 and H10) were associated with a low warfarin dose requirement (2.9 and 2.63 mg per day; p<0.01)) while H6 and H7 were associated with high dose requirement (4.55 and 4.83 mg per day; p<0.01). The average INR was approximately 2.4 and did not differ significantly among the patients classified according to VKORC1 haplotype combination (P value=0.196). The multiple regression analysis (Enter method) indicated that VKORC1 accounted for 24.8 % the variation in warfarin dose. Conclusion: VKORC1 haplotype provided a good correlation for different warfarin dose requirements. Genotyping of patients before warfarin is thus useful to predict more accurately dose required. Corresponding author: M. Z. Salleh, Head, Pharmacogenomics Centre, Faculty of Pharmacy, Universiti Teknologi MARA Malaysia. Acknowledgement: This study was supported by kecermerlangan’s UiTM.
format	Conference or Workshop Item
author	Beshna, E Teh , Lay Kek Ngow, Harris Abdullah Harun, Roslan Salleh, Mohd Zaki
author_facet	Beshna, E Teh , Lay Kek Ngow, Harris Abdullah Harun, Roslan Salleh, Mohd Zaki
author_sort	Beshna, E
title	VKORC1 Haplotypes in patients treated with warfarin
title_short	VKORC1 Haplotypes in patients treated with warfarin
title_full	VKORC1 Haplotypes in patients treated with warfarin
title_fullStr	VKORC1 Haplotypes in patients treated with warfarin
title_full_unstemmed	VKORC1 Haplotypes in patients treated with warfarin
title_sort	vkorc1 haplotypes in patients treated with warfarin
publishDate	2010
url	http://irep.iium.edu.my/5241/ http://irep.iium.edu.my/5241/1/Pharmacogenomic_VKROC1_Halotype_Abstract_Poster.pdf
first_indexed	2023-09-18T20:13:44Z
last_indexed	2023-09-18T20:13:44Z
_version_	1777407648582336512

VKORC1 Haplotypes in patients treated with warfarin

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