A New Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for Haplotyping of VKORC1 Gene to Predict Warfarin Sensitivity

The vitamin K epoxide reductase complex 1 gene (VKORC1) is commonly assessed to predict warfarin sensitivity. In this study, a new nested allele-specific multiplex polymerase chain reaction (PCR) method that can simultaneously identify single nucleotide polymorphisms (SNPs) at VKORC1 381, 861, 580...

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Main Authors: Yung, An Chua, Abdullah, Wan Zaidah, Yusof, Zukurnai, Siew, Hua Gan
Format: Article
Language:English
Published: Hindawi Publishing Corporation 2014
Subjects:
Online Access:http://eprints.usm.my/38067/
http://eprints.usm.my/38067/1/A_New_Nested_Allele-Specific_Multiplex_Polymerase_Chain_Reaction_Method_for.pdf
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author Yung, An Chua
Abdullah, Wan Zaidah
Yusof, Zukurnai
Siew, Hua Gan
author_facet Yung, An Chua
Abdullah, Wan Zaidah
Yusof, Zukurnai
Siew, Hua Gan
author_sort Yung, An Chua
building USM Institutional Repository
collection Online Access
description The vitamin K epoxide reductase complex 1 gene (VKORC1) is commonly assessed to predict warfarin sensitivity. In this study, a new nested allele-specific multiplex polymerase chain reaction (PCR) method that can simultaneously identify single nucleotide polymorphisms (SNPs) at VKORC1 381, 861, 5808, and 9041 for haplotype analysiswas developed and validated. ExtractedDNAwas amplified in the first PCR DNA, which was optimized by investigating the effects of varying the primer concentrations, annealing temperature, magnesium chloride concentration, enzyme concentration, and the amount of DNA template. The amplification products produced from the first round of PCR were used as templates for a second PCR amplification in which both mutant and wild-type primers were added in separate PCR tubes, followed by optimization in a similar manner. The final PCR products were resolved by agarose gel electrophoresis and further analysed by using a VKORC1 genealogic tree to infer patient haplotypes. Fifty patients were identified to have H1H1, one had H1H2, one had H1H7, 31 had either H1H7 or H1H9, one had H1H9, eight had H7H7, and one had H8H9 haplotypes. This is the first method that is able to infer VKORC1 haplotypes using only conventional PCR methods.
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spelling usm-380672017-12-22T02:18:33Z http://eprints.usm.my/38067/ A New Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for Haplotyping of VKORC1 Gene to Predict Warfarin Sensitivity Yung, An Chua Abdullah, Wan Zaidah Yusof, Zukurnai Siew, Hua Gan RM Therapeutics. Pharmacology The vitamin K epoxide reductase complex 1 gene (VKORC1) is commonly assessed to predict warfarin sensitivity. In this study, a new nested allele-specific multiplex polymerase chain reaction (PCR) method that can simultaneously identify single nucleotide polymorphisms (SNPs) at VKORC1 381, 861, 5808, and 9041 for haplotype analysiswas developed and validated. ExtractedDNAwas amplified in the first PCR DNA, which was optimized by investigating the effects of varying the primer concentrations, annealing temperature, magnesium chloride concentration, enzyme concentration, and the amount of DNA template. The amplification products produced from the first round of PCR were used as templates for a second PCR amplification in which both mutant and wild-type primers were added in separate PCR tubes, followed by optimization in a similar manner. The final PCR products were resolved by agarose gel electrophoresis and further analysed by using a VKORC1 genealogic tree to infer patient haplotypes. Fifty patients were identified to have H1H1, one had H1H2, one had H1H7, 31 had either H1H7 or H1H9, one had H1H9, eight had H7H7, and one had H8H9 haplotypes. This is the first method that is able to infer VKORC1 haplotypes using only conventional PCR methods. Hindawi Publishing Corporation 2014 Article PeerReviewed application/pdf en http://eprints.usm.my/38067/1/A_New_Nested_Allele-Specific_Multiplex_Polymerase_Chain_Reaction_Method_for.pdf Yung, An Chua and Abdullah, Wan Zaidah and Yusof, Zukurnai and Siew, Hua Gan (2014) A New Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for Haplotyping of VKORC1 Gene to Predict Warfarin Sensitivity. BioMed Research International , 2014 (316310). pp. 1-6. ISSN 2314-6133 http://dx.doi.org/10.1155/2014/316310
spellingShingle RM Therapeutics. Pharmacology
Yung, An Chua
Abdullah, Wan Zaidah
Yusof, Zukurnai
Siew, Hua Gan
A New Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for Haplotyping of VKORC1 Gene to Predict Warfarin Sensitivity
title A New Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for Haplotyping of VKORC1 Gene to Predict Warfarin Sensitivity
title_full A New Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for Haplotyping of VKORC1 Gene to Predict Warfarin Sensitivity
title_fullStr A New Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for Haplotyping of VKORC1 Gene to Predict Warfarin Sensitivity
title_full_unstemmed A New Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for Haplotyping of VKORC1 Gene to Predict Warfarin Sensitivity
title_short A New Nested Allele-Specific Multiplex Polymerase Chain Reaction Method for Haplotyping of VKORC1 Gene to Predict Warfarin Sensitivity
title_sort new nested allele-specific multiplex polymerase chain reaction method for haplotyping of vkorc1 gene to predict warfarin sensitivity
topic RM Therapeutics. Pharmacology
url http://eprints.usm.my/38067/
http://eprints.usm.my/38067/
http://eprints.usm.my/38067/1/A_New_Nested_Allele-Specific_Multiplex_Polymerase_Chain_Reaction_Method_for.pdf