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

Abstract

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 CYP2D6*3, CYP2D6*4, CYP2C9*2, CYP2C9*3 and CYP3A5*3 allelic variants by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method, CYP2C19*2 and CYP2C19*3 with allelic specific amplification (PCR-ASA), and CYP2D6*2 (gene duplications) by long PCR analysis. The allelic frequencies (out of a total of 566 alleles) for CYP2D6*3 and CYP2D6*4, were 2.3% and 17.8%, respectively, while gene duplications (CYP2D6*2) were found in 7.4% of the subjects tested. For CYP2C9*2 and CYP2C9*3 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 CYP2C19*3 allele. Finally, the CYP3A5*3 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.

Frequency of common CYP3A5 gene variants in healthy Polish newborn infants

“…Highly similar frequencies were observed for German, Finnish, Swedish and Greek populations [2,7,11,14,17,22]. Interestingly, the allelic frequencies described in our work are not significantly different from the ones published for the Baltic Sea area.…”

“…Gene variants of CYP3A5 are responsible for major individual differences in enzymatic activity, strongly influencing pharmacokinetics and bioavailability of an array of drugs with a narrow therapeutic window, as well as the individual response to the drug therapy [2,5,15]. The most frequent single nucleotide polymorphism (SNP) of functional importance in the CYP3A5 gene is the A to G transition in intron 3 at position 6986 (CYP3A5*3) [17].…”

Testing for variants in CYP2C19: population frequencies and testing experience in a clinical laboratory

“…These include Brazil, 35 Iran, 36,37 East Asia, 38 Ghana, 39 United States Ashkenazi Jews, 40 Greece, 41 Mexican Americans, 42 Bolivia, 43 Israel, 44 Malaysia, 45 Egypt, 46 and whites of European descent. 47 However, these studies were limited to a small number of deficiency alleles and did not include the *17 gain-of-function allele.…”

Intervention of Pharmacogenetic Profiling in Therapeutics of Kashmiri Population, a Lesson Learned From Cyp3a5*3 Variant

“…Pharmacogenetic studies have revealed the essence of polymorphism in drug metabolizing enzymes, transporters and receptors which contribute to variable drug response as per the individual's genetic makeup (Eichelbaum et al, 2006). CYP3A5 is forms are responsible for metabolizing about 50% of all clinically approved drugs (Arvanitidas et al, 2007). Thus polymorphism of CYP family may have most impact on the fate of these and other therapeutic drugs whose metabolism they regulate.…”