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Caraco Y, Leitersdorf E, Levy M, et al. Phenotypic-genotypic analysis of CYP2C19 in the Jewish Israeli population. Clin Pharmacol Ther. 1999;65(3):275-82doi: 10.1016/S0009-9236(99)70106-2.
Caraco, Y., Leitersdorf, E., Levy, M., Shpizen, S., & Sviri, S. (1999). Phenotypic-genotypic analysis of CYP2C19 in the Jewish Israeli population. Clinical pharmacology and therapeutics, 65(3), 275-82. https://doi.org/10.1016/S0009-9236(99)70106-2
Caraco, Y, et al. "Phenotypic-genotypic analysis of CYP2C19 in the Jewish Israeli population." Clinical pharmacology and therapeutics vol. 65,3 (1999): 275-82. doi: https://doi.org/10.1016/S0009-9236(99)70106-2
Caraco Y, Leitersdorf E, Levy M, Shpizen S, Sviri S. Phenotypic-genotypic analysis of CYP2C19 in the Jewish Israeli population. Clin Pharmacol Ther. 1999 Mar;65(3):275-82. doi: 10.1016/S0009-9236(99)70106-2. PMID: 10096259.
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Clin Pharmacol Ther. 1999 Mar;65(3):275-82. doi: 10.1016/S0009-9236(99)70106-2.

Phenotypic-genotypic analysis of CYP2C19 in the Jewish Israeli population.

Clinical pharmacology and therapeutics

Y Caraco, E Leitersdorf, M Levy, S Shpizen, S Sviri

Affiliations

  1. Division of Medicine, the Center of Research, Prevention and Treatment of Atherosclerosis, Hadassah University Hospital, Jerusalem, Israel.

PMID: 10096259 DOI: 10.1016/S0009-9236(99)70106-2

Abstract

OBJECTIVES: Evaluation of CYP2C19 activity and the frequency of CYP2C19 alleles in the Jewish Israeli population.

METHODS: One hundred forty Jewish Israeli subjects received 100 mg racemic mephenytoin and collected urine for 8 hours. Urinary concentrations of mephenytoin enantiomers and 4'-hydroxymephenytoin were determined by gas-liquid chromatography and HPLC, respectively. CYP2C19 activity was derived from urinary S/R-ratio and 8-hour urinary excretion of 4'-hydroxymephenytoin. Mutations were identified by polymerase chain reaction and enzyme digestion with SmaI (CYP2C19*2) and BamHI (CYP2C19*3).

RESULTS: Deficient mephenytoin hydroxylation was found in 4 subjects (2.9%; 95% confidence interval [CI], 0.1% to 5.7%) who were homozygous for CYP2C19*2. CYP2C19*2 was the major deactivating allele accounting for 15% (95% CI, 11% to 19%) of CYP2C19 alleles, whereas CYP2C19*3 was identified in 2 subjects (1%; 95% CI, 0% to 2%). Among 136 extensive metabolizers, 99 were homozygous for CYP2C19*1 and 37 were compound heterozygous CYP2C19*1/CYP2C19*2 (35 subjects) or CYP2C19*1/CYP2C19*3 (2 subjects). Gene dose effect was noted so that the S/R-ratio was significantly greater and urinary excretion of 4'-hydroxymephenytoin was significantly lower in compound heterozygous than in homozygous extensive metabolizers (0.310+/-0.209 versus 0.225+/-0.176, P < .04 and 48.6%+/-19.2% versus 56.3%+/-16.0%, P < .03, respectively). Female extensive metabolizers had a significantly lower excretion of 4'-hydroxymephenytoin than male extensive metabolizers (49.5%+/-17.6% versus 58.4%+/-16.7%, respectively, P < .005).

CONCLUSION: The frequency of poor metabolizers of CYP2C19 and CYP2C19*2 allele in the Jewish Israeli population resembles findings in non-Asian populations. Complete concordance was noted between phenotypic and genotypic findings. CYP2C19 genotyping may enable subclassification of extensive metabolizers into subjects with high and low activity.

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