Genetic polymorphism of CYP2D6 and CYP2C19 metabolism determined by phenotyping Israeli ethnic groups

Genetic polymorphism of the cytochrome P450 isoenzymes CYP2D6 and CYP2C19 w as determined by phenotyping four ethnic groups of the Israeli population. The groups consisted of Ethiopian subjects, Yemenite subjects, and Russian subjects representing first-generation new immigrants and an Israeli Arab g roup. Dextromethorphan was used as the probe for CYP2D6 activity and mephen ytoin was used for CYP2C19 activity. The two drugs were administered simult aneously and urine samples were collected over a period of 8 hours. The CYP 2D6 phenotype was determined from the ratio of dextromethorphan conversion to dextrorphan and the CYP2C19 phenotype from the ratio of S-mephenytoin an d R-mephenytoin. The used liquid chromatographic method was able to complet ely separate dextrorphan and dextromethorphan. Fluorescence detection allow ed dextromethorphan quantification at 1 ng/mL. Mephenytoin enantiomers were completely separated in high-performance liquid chromatography and the res pective fractions were collected and analyzed using a gas chromatography/ma ss spectrometry system with selective ion monitoring. The prevalence of poo r metabolizer phenotype of dextromethorphan (CYP2D6) in the Yemenite (0%) a nd Ethiopian groups (0%) was significantly different from the prevalence in the Russian (17%) and Israeli Arab (9%) groups. A significant difference w as also found in the distribution of the metabolic ratio of the extensive m etabolizer phenotype between the Ethiopian group and the Russian and Yemeni te groups. No significant difference was found in the prevalence of poor me phenytoin metabolizer phenotype (CYP2C19) between the Yemenite (8%), Ethiop ian (6%), Russian (9%), and Israeli Arab (8%) groups. No difference was obs erved in the distribution of metabolic ratio within the extensive metaboliz er phenotype subgroups of the four ethnic groups.