Genetic polymorphisms of drug-metabolizing enzymes CYP2D6, CYP2C9, CYP2C19 and CYP3A5 in the Greek population.

The aim of the present study was to determine the prevalence of the most common allelic variants of the polymorphic cytochrome P450 (CYP) enzymes CYP2D6, CYP2C9, CYP2C19 and CYP3A5 and to predict the genotype frequency for each polymorphism in the Greek population. DNA isolated from peripheral blood samples derived from 283 non-related Greek ethnic subjects was used to determine the frequency of CYP2D63, CYP2D64, CYP2C92, CYP2C93 and CYP3A53 allelic variants by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method, CYP2C192 and CYP2C193 with allelic specific amplification (PCR-ASA), and CYP2D62 (gene duplications) by long PCR analysis. The allelic frequencies (out of a total of 566 alleles) for CYP2D63 and CYP2D64, were 2.3% and 17.8%, respectively, while gene duplications (CYP2D62) were found in 7.4% of the subjects tested. For CYP2C92 and CYP2C93 polymorphisms the allelic frequencies were 12.9% and 8.13% respectively. For CYP2C19, the 2 polymorphism was present at an allelic frequency of 13.1%, while no subjects were found carrying the CYP2C193 allele. Finally, the CYP3A53 allele was abundantly present in the Greek population with an allelic frequency of 94.4%. Overall our results show that the frequencies of the common defective allelic variants of CYP2C9, CYP2C19 and CYP3A5 in Greek subjects are similar to those reported for several other Caucasian populations. Finally, a high prevalence of CYP2D6 gene duplication among Greeks was found, a finding that strengthens the idea that a South/North gradient exists in the occurrence of CYP2D6 ultrarapid metabolizers in European populations.