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Prevalence of CYP2C9 polymorphisms in the south of Europe

The Pharmacogenomics Journal volume 9, pages 306–310 (2009)Cite this article

A Corrigendum to this article was published on 21 May 2010

Abstract

CYP2C9 is a major liver enzyme responsible of the metabolism of many clinically important drugs. The presence of CYP2C9 genetic polymorphisms has been associated with marked interindividual variability in its catalytic activity that could result in drug toxicity. Here we present frequencies of the most common CYP2C9 coding variants CYP2C9*2 (C430T) and CYP2C9*3 (A1075C) in representative samples of four regions from Spain (Basque Country, n=358; Catalonia, n=240; Central Spain, n=190 and Galicia, n=288) and one northern Italian region, (Verona, n=164), which range between 0.125 and 0.165 in the case of CYP2C9*2 and between 0.071 and 0.085 for CYP2C9*3. No significant differences between CYP2C9 allele frequencies were found comparing all the sampled populations. A more extensive comparative analysis using allele frequency data of populations widely spread over Europe was performed, showing significant differences in the CYP2C9*2 allele frequencies distribution between some of the regions, being quite homogeneous in the case of CYP2C9*3 variant. The results obtained show that above 40% of our samples carry a mutate allele, which can result in a poor metabolization of low therapeutic index drugs as oral anticoagulants (warfarin, acenocoumarol), oral antidiabetic drugs and some non-steroidal anti-inflammatory drugs. Our study constitutes both a large (n=1240) and robust allele frequency database on CYP2C9 polymorphisms, which represents one of the most numerous CYP2C9*2 and *3 database existing to date.

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Acknowledgements

This study was supported by grants PI021512, PI021364, PI020661, PI021572 (Health Research Fund, Fondo de Investigación Sanitaria, Spain), SAF2002-04057 (Ministry of Health and Consumer Affairs, Spain), PGIDIT03PXIC20806PN (Xunta de Galicia, Spain) and 02/1572 (Basque Regional Authority, Spain). PSD is supported by the Isidro Parga Pondal program (Plan Galego de Investigación, Desenvolvemento e Innovación Tecnolóxica-INCITE (2006–2010) from Xunta de Galicia, Spain). The Diana Fundación Barrié-USC Research Program (Fundación Pedro Barrié de la Maza) has partially funded this study. We express our gratitude to Enrique Domínguez, Antía Romaní Fernández, María Jose López Otero, Alberto Ruano and Juan Miguel Barros Dios from the Santiago de Compostela University Clinical Teaching Hospital, and Elena Ballarín, Xavier Barroso, Cristina Rebordosa, Lourdes Vendrell and Soraya Martín from Hospital Vall d’ Hebron of Barcelona. We are also grateful to María Brión and Angel Salgado Barreiro for their help and comments.

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Authors and Affiliations

  1. Genomics Medicine Group, Institute of Legal Medicine, University of Santiago de Compostela, CIBER for Rare Diseases (CIBERER), Santiago de Compostela, Spain

    Paula Sánchez-Diz & Angel Carracedo

  2. Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain

    Ana Estany-Gestal & Adolfo Figueiras

  3. Unidad de Farmacovigilancia, Hospital de Galdakao-Usansolo, Bilbao, Spain

    Carmelo Aguirre & Borja Ruiz

  4. Unit of Molecular Hematologic Genetics, Clinical Laboratories, Hospital Vall d'Hebron, Barcelona, Spain

    Adoración Blanco

  5. Catalan Institute of Pharmacology, Clinical Pharmacology Service, University Hospital Vall d'Hebron, Barcelona, Spain

    Luisa Ibáñez

  6. Department of Pharmacology, Therapeutics and Toxicology, Autonomous University, Barcelona, Spain

    Luisa Ibáñez

  7. Department of Medicine and Public Health, Section of Pharmacology, University of Verona, Verona, Italy

    Marianna Passiu

  8. Department of Mother and Child, Section of Biology and Genetics, University of Verona, Verona, Italy

    Lisa Provezza

  9. “Toñi Martín Gallardo” Genomics Unit, Science Park of Madrid, Madrid, Spain

    Ricardo Ramos-Ruiz

  10. Cancer Genetics, Institute of Biology and Molecular Genetics (UVa-CSIC), Valladolid, Spain

    Inés Salado-Valdivieso

  11. Instituto de Farmacoepidemiología, Universidad de Valladolid, Valladolid, Spain

    Eladio A Velasco

  12. Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP),

    Adolfo Figueiras

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  1. Paula Sánchez-Diz
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  2. Ana Estany-Gestal
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Correspondence to Paula Sánchez-Diz.

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Sánchez-Diz, P., Estany-Gestal, A., Aguirre, C. et al. Prevalence of CYP2C9 polymorphisms in the south of Europe. Pharmacogenomics J 9, 306–310 (2009). https://doi.org/10.1038/tpj.2009.16

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  • DOI: https://doi.org/10.1038/tpj.2009.16

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