title: Prevalence of CYP2C9 polymorphisms in the south of Europe.
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.
authors.affiliation: Genomics Medicine Group, Institute of Legal Medicine, University of Santiago de Compostela, CIBER for Rare Diseases (CIBERER), 15782 Santiago de Compostela, Spain. paula.sanchez@usc.es
authors.forename: Paula
authors.initials: P
authors.lastname: Sánchez-Diz
authors.forename: Ana
authors.initials: A
authors.lastname: Estany-Gestal
authors.forename: Carmelo
authors.initials: C
authors.lastname: Aguirre
authors.forename: Adoración
authors.initials: A
authors.lastname: Blanco
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: Luisa
authors.initials: L
authors.lastname: Ibáñez
authors.forename: Marianna
authors.initials: M
authors.lastname: Passiu
authors.forename: Lisa
authors.initials: L
authors.lastname: Provezza
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ramos-Ruiz
authors.forename: Borja
authors.initials: B
authors.lastname: Ruiz
authors.forename: Inés
authors.initials: I
authors.lastname: Salado-Valdivieso
authors.forename: Eladio A
authors.initials: EA
authors.lastname: Velasco
authors.forename: Adolfo
authors.initials: A
authors.lastname: Figueiras
mesh_terms: D024506:5' Flanking Region; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D001711:Biotransformation / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D030541:Databases, Genetic; D005787:Gene Frequency; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008099:Liver / Q000201:enzymology*; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D013030:Spain
chemical_list: C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases