Clinical Chemistry
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Clinical Chemistry 55: 823-826, 2009. First published February 20, 2009; 10.1373/clinchem.2008.118497
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(Clinical Chemistry. 2009;55:823-826.)
© 2009 American Association for Clinical Chemistry, Inc.

Brief Communication

A Multiplex Assay for Detecting Genetic Variations in CYP2C9, VKORC1, and GGCX Involved in Warfarin Metabolism

Alex J. Rai1,2,a, Nitin Udar3, Rana Saad4 and Martin Fleisher1

1 Departments of Clinical Laboratories and 2 Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY; 3 Beckman Coulter, Fullerton, CA; 4 Department of Pathology, Baylor University Medical Center, Dallas, TX;

aaddress correspondence to this author at: Department of Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 88, New York, NY 10065. Fax 212-717 3397; e-mail raia{at}mskcc.org.


Abstract

Background: Patients differ in responses to warfarin, which is commonly prescribed to treat thromboembolic events. Genetic variations in the cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9), vitamin K epoxide reductase complex, subunit 1 (VKORC1), and gamma-glutamyl carboxylase (GGCX) genes have been shown to contribute to impaired metabolism of warfarin.

Methods: We designed a custom multiplex single-nucleotide polymorphism (SNP) panel to interrogate the CYP2C9 *2, *3, VKORC1 (–1639G->A), and GGCX (1181T->G) alleles simultaneously in a single sample by use of single-base extension and capillary electrophoresis after genomic DNA extraction and PCR amplification.

Results: Our assay successfully detected various genotypes from known controls and 24 unknown samples. It was found to be 100% concordant with sequencing results.

Conclusions: Our multiplexed SNP panel can be successfully used in genotyping of patient blood samples. Results can be combined with other clinical parameters in an algorithm for warfarin dosing. These data provide a proof-in-principle of multiplexed SNP analysis using rapid single-base extension and capillary electrophoresis, and warrant additional validation using a larger cohort of patient samples.






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Copyright © 2009 by the American Association for Clinical Chemistry.