Need for Reassessment of Reported CYP2C19 Allele Frequencies in Various Populations in View of CYP2C19*17 Discovery: The Case of Greece

Abstract

CYP2C19*17 is a novel variant allele causing ultrarapid metabolism of CYP2C19 substrates. In the present study we investigated the CYP2C19*17 allelic frequency and recalculated previously reported frequencies of the CYP2C19*1/*1 genotype and of all genotype-derived phenotypes for CYP2C19 in the Greek population. A total of 283 nonrelated healthy Greek ethnic subjects that had already been genotyped for CYP2C19*2 and *3 alleles as well as for CYP2D6 and CYP2C9 variant alleles participated in the study. The CYP2C19*17 allele was genotyped by the PCR-RFLP method. The CYP2C19*17 allele frequency was 19.61%. The prevalence of CYP2C19*17 carriers in the Greek population was estimated at 31.80%, while the frequency of CYP2C19*1/*1 genotype was recalculated to 44.17% from 75.97% in our previous study. Several subjects possessing both CYP2C19*17 and variant alleles of CYP2D6 and CYP2C9 were also identified. The CYP2C19*17 allele is present in Greeks at a high frequency similar to that found in other European populations of Caucasian origin. Our study highlights the need of reassessing and updating CYP2C19 allelic frequencies in various populations in view of the major role that CYP2C19*17 may have in predicting the clinical outcome of drugs metabolized by CYP2C19.