Copy number variation and warfarin dosing: evaluation of CYP2C9, VKORC1, CYP4F2, GGCX and CALU by Scott Stuart A, Patel Manishkumar, Martis Suparna, Lubitz Steven A, van der Zee Sarina, Yoo Chang, Edelmann Lisa, Halperin Jonathan L, Desnick Robert J in Pharmacogenomics (2011).

[PMID: 22188360] PubMed


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.

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