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 CYP2C19*1, *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 CYP2C19*4 and CYP2D6*41A alleles in the AJ population resulted in the clinically relevant reclassification of the predicted metabolizer phenotypes. Inclusion of CYP2C19*4 reclassified individuals from either extensive- or intermediate- to the intermediate- or poor-metabolizer phenotypes, respectively. Inclusion of the redefined CYP2D6*41A 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.
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 CYP2C19*1, *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 CYP2C19*4 and CYP2D6*41A alleles in the AJ population resulted in the clinically relevant reclassification of the predicted metabolizer phenotypes. Inclusion of CYP2C19*4 reclassified individuals from either extensive- or intermediate- to the intermediate- or poor-metabolizer phenotypes, respectively. Inclusion of the redefined CYP2D6*41A 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.
Authors: I Fricke-Galindo; C Céspedes-Garro; F Rodrigues-Soares; M E G Naranjo; Á Delgado; F de Andrés; M López-López; E Peñas-Lledó; A LLerena Journal: Pharmacogenomics J Date: 2015-10-27 Impact factor: 3.550
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Authors: Raymon Vijzelaar; Mariana R Botton; Lisette Stolk; Suparna Martis; Robert J Desnick; Stuart A Scott Journal: Pharmacogenomics Date: 2018-05-23 Impact factor: 2.533
Authors: M E G Naranjo; F de Andrés; A Delgado; J Cobaleda; E M Peñas-Lledó; A LLerena Journal: Pharmacogenomics J Date: 2016-06-07 Impact factor: 3.550
Authors: Stuart A Scott; Aniwaa Owusu Obeng; Mariana R Botton; Yao Yang; Erick R Scott; Stephen B Ellis; Richard Wallsten; Tom Kaszemacher; Xiang Zhou; Rong Chen; Paola Nicoletti; Hetanshi Naik; Eimear E Kenny; Aida Vega; Eva Waite; George A Diaz; Joel Dudley; Jonathan L Halperin; Lisa Edelmann; Andrew Kasarskis; Jean-Sébastien Hulot; Inga Peter; Erwin P Bottinger; Kurt Hirschhorn; Pamela Sklar; Judy H Cho; Robert J Desnick; Eric E Schadt Journal: Pharmacogenomics Date: 2017-10-06 Impact factor: 2.533