BackgroundThe cytochrome P450 isoenzymes CYP2C19 and CYP2D6 catalyze reactions involved in the metabolism of many widely used drugs. Their polymorphisms give rise to important interindividual and interethnic variability in the metabolism and disposition of several therapeutic agents and may cause differences in clinical response to some drugs. Individuals who carry two null alleles of either gene are known as poor metabolizers (PMs), while those who carry more than two copies of the functionalCYP2D6gene are ultrarapid metabolizers (UMs).AimThe aim of the current study was to genotype Israelis from four different ethnic backgrounds with respect toCYP2C19andCYP2D6.Study designPolymorphisms of theCYP2C19andCYP2D6genes were determined by genotyping the four ethnic groups using PCR and/or restriction fragment length polymorphism (RFLP) analysis. The groups consisted of three Jewish communities, Yemenite Jews ( n = 36), Sephardic Jews (n = 47), Ethiopian Jews (n = 28), and one Arabian population, Bedouins (n = 50).ResultsCYP2C19*2 allele frequencies ranged from 12.0 to 19.6% among the four ethnic groups. Within the study population, theCYP2C19*3 gene was only found in one Bedouin individual, in the heterozygous state (CYP2C19*1/*3). In each group, one individual was homozygous forCYP2C19*2, and were predicted to be PMs. The data revealed a high prevalence ofCYP2D6*2, *4, *10, *41, and gene duplication, followed by *5 and *17, while *3 was very rare. The frequencies of theCYP2D6*4, *10, and *17 alleles andCYP2D6gene duplication were significantly different among the four groups. However, theCYP2D6*2, *3, and *5 and *41 alleles showed similar frequencies in the four groups. Four (8.5%) Sephardic Jews and one (2.0%) Bedouin were found with the genotypeCYP2D6*4/*4 (two null alleles), and were thus presumably PMs. A total of 15 individuals, distributed in all groups, were found with functionalCYP2D6gene duplications. The frequencies of predicted UMs (duplication ofCYP2D6) were 17.8% (5/28) and 12.8% (6/47) in Ethiopian Jews and Sephardic Jews, respectively, which were higher than that of Yemenite Jews (5.6%, 2/36) and Bedouins (4.0%, 2/50).ConclusionsThis is the first study of theCYP2D6gene polymorphism in Israeli ethnic groups, either Jewish or Arab. Furthermore, this is also the first study of theCYP2C19gene polymorphism in Jewish or Arab subgroups living in Israel. The frequencies of various alleles for theCYP2D6gene are significantly different among the ethnic groups in Israel. These new findings may have important clinical implications in administrating drugs metabolized by CYP2D6 and for CYP2D6-related adverse drug reactions in the Israeli population.