Prevalence of CYP2C9 polymorphisms in the south of Europe

• Published in: The pharmacogenomics journal Vol. 9; no. 5; pp. 306 - 310
• Main Authors: Sánchez-Diz, Paula, Estany-Gestal, Ana, Aguirre, Carmelo, Blanco, Adoración, Carracedo, Angel, Ibáñez, Luisa, Passiu, Marianna, Provezza, Lisa, Ramos-Ruiz, Ricardo, Ruiz, Borja, Salado-Valdivieso, Inés, Velasco, Eladio A, Figueiras, Adolfo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-10-2009; Nature Publishing Group
• Subjects: 5' Flanking Region; Alleles; Anticoagulants; Anticoagulants (Medicine); Antidiabetics; Aryl Hydrocarbon Hydroxylases - genetics; Aryl Hydrocarbon Hydroxylases - metabolism; Biomedical and Life Sciences; Biomedicine; Biotransformation - genetics; Comparative analysis; Complications and side effects; Cytochrome P-450 CYP2C9; Databases, Genetic; Diabetes mellitus; Distribution; Dosage and administration; Drug metabolism; Drugs; Gene Expression; Gene Frequency; Gene polymorphism; Genetic polymorphisms; Genetics, Population; Haplotypes; Human Genetics; Humans; Inflammation; Italy; Linkage Disequilibrium; Liver - enzymology; Nonsteroidal anti-inflammatory drugs; Oncology; original-article; Pharmacotherapy; Polymorphism, Single Nucleotide; Population genetics; Psychopharmacology; Reproducibility of Results; Spain; Toxicity; Italy; Spain; Europe; Italy; CYP2C9 5′-flanking region; CYP2C9 polymorphism; allele frequency; Spain
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2009.16

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.