Copy number variation and warfarin dosing: evaluation of CYP2C9, VKORC1, CYP4F2, GGCX and CALU
| Autor: | Jonathan L. Halperin, Robert J. Desnick, Steven A. Lubitz, Lisa Edelmann, Sarina van der Zee, Manishkumar Patel, Stuart A. Scott, Suparna Martis, Chang Yoo |
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| Rok vydání: | 2011 |
| Předmět: |
Male
DNA Copy Number Variations CYP4F2 Biology Article Mixed Function Oxygenases Cohort Studies Exon Cytochrome P-450 Enzyme System INDEL Mutation Gene Duplication Vitamin K Epoxide Reductases Genetics Ethnicity Humans Multiplex Copy-number variation Cytochrome P450 Family 4 CYP2C9 Aged Cytochrome P-450 CYP2C9 Pharmacology Dose-Response Relationship Drug Calcium-Binding Proteins Anticoagulants Exons Molecular biology Real-time polymerase chain reaction Carbon-Carbon Ligases Molecular Medicine Vitamin K epoxide reductase Female VKORC1 Aryl Hydrocarbon Hydroxylases Warfarin Gene Deletion |
| Zdroj: | Pharmacogenomics. 13(3) |
| ISSN: | 1744-8042 7166-8942 |
| Popis: | Aim: To determine if copy number variants contribute to warfarin dose requirements, we investigated CYP2C9, VKORC1, CYP4F2, GGCX and CALU for deletions and duplications in a multiethnic patient population treated with therapeutic doses of warfarin. Patients & methods: DNA samples from 178 patients were subjected to copy number analyses by multiplex ligation-dependent probe amplification or quantitative PCR assays. Additionally, the CYP2C9 exon 8 insertion/deletion polymorphism (rs71668942) was examined among the patient cohort and 1750 additional multiethnic healthy individuals. Results: All patients carried two copies of CYP2C9 by multiplex ligation-dependent probe amplification and no exon 8 deletion carriers were detected. Similarly, quantitative PCR assays for VKORC1, CYP4F2, GGCX and CALU identified two copies in all populations. Conclusion: These data indicate that copy number variants in the principal genes involved in warfarin dose variability (CYP2C9, VKORC1), including genes with lesser effect (CYP4F2, GGCX), and those that may be more relevant among certain racial groups (CALU), are rare in multiethnic populations, including African–Americans. Original submitted 5 August 2011; Revision submitted 26 October 2011 |
| Databáze: | OpenAIRE |
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