1. ¹Genomics Medicine Group, Institute of Legal Medicine, University of Santiago de Compostela, CIBER for Rare Diseases (CIBERER), Santiago de Compostela, Spain
2. ²Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain
3. ³Unidad de Farmacovigilancia, Hospital de Galdakao-Usansolo, Bilbao, Spain
4. ⁴Unit of Molecular Hematologic Genetics, Clinical Laboratories, Hospital Vall d'Hebron, Barcelona, Spain
5. ⁵Catalan Institute of Pharmacology, Clinical Pharmacology Service, University Hospital Vall d'Hebron, Barcelona, Spain
6. ⁶Department of Pharmacology, Therapeutics and Toxicology, Autonomous University, Barcelona, Spain
7. ⁷Department of Medicine and Public Health, Section of Pharmacology, University of Verona, Verona, Italy
8. ⁸Department of Mother and Child, Section of Biology and Genetics, University of Verona, Verona, Italy
9. ⁹"Toñi Martín Gallardo" Genomics Unit, Science Park of Madrid, Madrid, Spain
10. ¹⁰Cancer Genetics, Institute of Biology and Molecular Genetics (UVa-CSIC), Valladolid, Spain
11. ¹¹Instituto de Farmacoepidemiología, Universidad de Valladolid, Valladolid, Spain
12. ¹²Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP)

Correspondence: Dr P Sánchez-Diz, Genomics Medicine Group, Institute of Legal Medicine, University of Santiago de Compostela, c/San Francisco, s/n. 15782 Santiago de Compostela. A Coruña. Spain. E-mail: paula.sanchez@usc.es

Received 9 March 2009; Accepted 16 March 2009; Published online 21 April 2009.

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.