CYP2C9, CYP2C19 and CYP2D6 allele frequencies in the Ashkenazi Jewish population.

OBJECTIVE

To determine and compare the cytochrome P450 (CYP)2C9, CYP2C19 and CYP2D6 allele and genotype frequencies in the Ashkenazi Jewish (AJ) population with other populations.

METHODS

CYP2C9, CYP2C19 and CYP2D6 genotypes were determined in 250 anonymous, unrelated, healthy AJ individuals from the greater New York (USA) metropolitan area. Genotyping was performed using the Tag-Ittrade mark Mutation Detection system and the recently redefined CYP2D6*41A allele was identified by a restriction fragment length polymorphism assay.

RESULTS

Among the 250 AJ individuals, the CYP2C9*1, *2, *3 and 5 allele frequencies were 0.772, 0.140, 0.086 and 0.002, respectively, and the genotypes were distributed into extensive- (60.8%), intermediate- (32.8%) and poor- (6.4%) metabolizer phenotypes. The CYP2C191, *2 and *4 allele frequencies were 0.830, 0.152 and 0.018, respectively, and the genotypes were distributed into extensive (69.2%), intermediate (27.6%) and poor (3.2%) metabolizers. The most common CYP2D6 alleles identified were *1, *2A, *4 and *41A, and their frequencies were 0.286 0.152 0.226 and 0.140, respectively. The CYP2D6 genotypes were distributed into ultrarapid- (8.8%), extensive- (70.0%), intermediate- (16.0%) and poor- (5.2%) metabolizer phenotypes.

CONCLUSION

Although the CYP2C9 allele and genotype frequencies in the AJ subjects were similar to those in other North American Caucasian populations, genotyping the CYP2C194 and CYP2D641A alleles in the AJ population resulted in the clinically relevant reclassification of the predicted metabolizer phenotypes. Inclusion of CYP2C194 reclassified individuals from either extensive- or intermediate- to the intermediate- or poor-metabolizer phenotypes, respectively. Inclusion of the redefined CYP2D641A allele increased the ultrarapid-, intermediate- and poor-metabolizer phenotype combined frequencies to 30%, indicating that approximately one in three AJ individuals may benefit from genotype-based drug selection and dosage. In addition, the ultrarapid CYP2D6 genotype frequency in the AJ population (8.8%) was approximately twofold higher than that in other North American Caucasians.