Polymorphisms of CYP2C19 and CYP2D6 in Israeli ethnic groups

Huai Rong Luo, Vasileios Aloumanis, Keh Ming Lin, David Gurwitz, Yu-Jui Yvonne Wan

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: The 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 functional CYP2D6 gene are ultrarapid metabolizers (UMs). Aim: The aim of the current study was to genotype Israelis from four different ethnic backgrounds with respect to CYP2C19 and CYP2D6. Study design: Polymorphisms of the CYP2C19 and CYP2D6 genes 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). Results: CYP2C19*2 allele frequencies ranged from 12.0 to 19.6% among the four ethnic groups. Within the study population, the CYP2C19*3 gene was only found in one Bedouin individual, in the heterozygous state (CYP2C19*1/*3). In each group, one individual was homozygous for CYP2C19*2, and were predicted to be PMs. The data revealed a high prevalence of CYP2D6*2, *4, *10, *41, and gene duplication, followed by *5 and *17, while *3 was very rare. The frequencies of the CYP2D6*4, *10, and *17 alleles and CYP2D6 gene duplication were significantly different among the four groups. However, the CYP2D6*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 genotype CYP2D6*4/*4 (two null alleles), and were thus presumably PMs. A total of 15 individuals, distributed in all groups, were found with functional CYP2D6 gene duplications. The frequencies of predicted UMs (duplication of CYP2D6) 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). Conclusions: This is the first study of the CYP2D6 gene polymorphism in Israeli ethnic groups, either Jewish or Arab. Furthermore, this is also the first study of the CYP2C19 gene polymorphism in Jewish or Arab subgroups living in Israel. The frequencies of various alleles for the CYP2D6 gene 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.

Original languageEnglish (US)
Pages (from-to)395-401
Number of pages7
JournalAmerican Journal of PharmacoGenomics
Volume4
Issue number6
DOIs
StatePublished - 2004
Externally publishedYes

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Cytochrome P-450 CYP2D6
Ethnic Groups
Jews
Gene Duplication
Genes
Alleles
Cytochrome P-450 CYP2C19
Israel
Gene Frequency
Genotype
Pharmaceutical Preparations
Population
Drug-Related Side Effects and Adverse Reactions
Restriction Fragment Length Polymorphisms

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

Cite this

Polymorphisms of CYP2C19 and CYP2D6 in Israeli ethnic groups. / Luo, Huai Rong; Aloumanis, Vasileios; Lin, Keh Ming; Gurwitz, David; Wan, Yu-Jui Yvonne.

In: American Journal of PharmacoGenomics, Vol. 4, No. 6, 2004, p. 395-401.

Research output: Contribution to journalArticle

Luo, Huai Rong ; Aloumanis, Vasileios ; Lin, Keh Ming ; Gurwitz, David ; Wan, Yu-Jui Yvonne. / Polymorphisms of CYP2C19 and CYP2D6 in Israeli ethnic groups. In: American Journal of PharmacoGenomics. 2004 ; Vol. 4, No. 6. pp. 395-401.
@article{94bc4e4f181a460dab6a22c76b512765,
title = "Polymorphisms of CYP2C19 and CYP2D6 in Israeli ethnic groups",
abstract = "Background: The 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 functional CYP2D6 gene are ultrarapid metabolizers (UMs). Aim: The aim of the current study was to genotype Israelis from four different ethnic backgrounds with respect to CYP2C19 and CYP2D6. Study design: Polymorphisms of the CYP2C19 and CYP2D6 genes 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). Results: CYP2C19*2 allele frequencies ranged from 12.0 to 19.6{\%} among the four ethnic groups. Within the study population, the CYP2C19*3 gene was only found in one Bedouin individual, in the heterozygous state (CYP2C19*1/*3). In each group, one individual was homozygous for CYP2C19*2, and were predicted to be PMs. The data revealed a high prevalence of CYP2D6*2, *4, *10, *41, and gene duplication, followed by *5 and *17, while *3 was very rare. The frequencies of the CYP2D6*4, *10, and *17 alleles and CYP2D6 gene duplication were significantly different among the four groups. However, the CYP2D6*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 genotype CYP2D6*4/*4 (two null alleles), and were thus presumably PMs. A total of 15 individuals, distributed in all groups, were found with functional CYP2D6 gene duplications. The frequencies of predicted UMs (duplication of CYP2D6) 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). Conclusions: This is the first study of the CYP2D6 gene polymorphism in Israeli ethnic groups, either Jewish or Arab. Furthermore, this is also the first study of the CYP2C19 gene polymorphism in Jewish or Arab subgroups living in Israel. The frequencies of various alleles for the CYP2D6 gene 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.",
author = "Luo, {Huai Rong} and Vasileios Aloumanis and Lin, {Keh Ming} and David Gurwitz and Wan, {Yu-Jui Yvonne}",
year = "2004",
doi = "10.2165/00129785-200404060-00006",
language = "English (US)",
volume = "4",
pages = "395--401",
journal = "American Journal of PharmacoGenomics",
issn = "1175-2203",
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T1 - Polymorphisms of CYP2C19 and CYP2D6 in Israeli ethnic groups

AU - Luo, Huai Rong

AU - Aloumanis, Vasileios

AU - Lin, Keh Ming

AU - Gurwitz, David

AU - Wan, Yu-Jui Yvonne

PY - 2004

Y1 - 2004

N2 - Background: The 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 functional CYP2D6 gene are ultrarapid metabolizers (UMs). Aim: The aim of the current study was to genotype Israelis from four different ethnic backgrounds with respect to CYP2C19 and CYP2D6. Study design: Polymorphisms of the CYP2C19 and CYP2D6 genes 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). Results: CYP2C19*2 allele frequencies ranged from 12.0 to 19.6% among the four ethnic groups. Within the study population, the CYP2C19*3 gene was only found in one Bedouin individual, in the heterozygous state (CYP2C19*1/*3). In each group, one individual was homozygous for CYP2C19*2, and were predicted to be PMs. The data revealed a high prevalence of CYP2D6*2, *4, *10, *41, and gene duplication, followed by *5 and *17, while *3 was very rare. The frequencies of the CYP2D6*4, *10, and *17 alleles and CYP2D6 gene duplication were significantly different among the four groups. However, the CYP2D6*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 genotype CYP2D6*4/*4 (two null alleles), and were thus presumably PMs. A total of 15 individuals, distributed in all groups, were found with functional CYP2D6 gene duplications. The frequencies of predicted UMs (duplication of CYP2D6) 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). Conclusions: This is the first study of the CYP2D6 gene polymorphism in Israeli ethnic groups, either Jewish or Arab. Furthermore, this is also the first study of the CYP2C19 gene polymorphism in Jewish or Arab subgroups living in Israel. The frequencies of various alleles for the CYP2D6 gene 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.

AB - Background: The 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 functional CYP2D6 gene are ultrarapid metabolizers (UMs). Aim: The aim of the current study was to genotype Israelis from four different ethnic backgrounds with respect to CYP2C19 and CYP2D6. Study design: Polymorphisms of the CYP2C19 and CYP2D6 genes 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). Results: CYP2C19*2 allele frequencies ranged from 12.0 to 19.6% among the four ethnic groups. Within the study population, the CYP2C19*3 gene was only found in one Bedouin individual, in the heterozygous state (CYP2C19*1/*3). In each group, one individual was homozygous for CYP2C19*2, and were predicted to be PMs. The data revealed a high prevalence of CYP2D6*2, *4, *10, *41, and gene duplication, followed by *5 and *17, while *3 was very rare. The frequencies of the CYP2D6*4, *10, and *17 alleles and CYP2D6 gene duplication were significantly different among the four groups. However, the CYP2D6*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 genotype CYP2D6*4/*4 (two null alleles), and were thus presumably PMs. A total of 15 individuals, distributed in all groups, were found with functional CYP2D6 gene duplications. The frequencies of predicted UMs (duplication of CYP2D6) 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). Conclusions: This is the first study of the CYP2D6 gene polymorphism in Israeli ethnic groups, either Jewish or Arab. Furthermore, this is also the first study of the CYP2C19 gene polymorphism in Jewish or Arab subgroups living in Israel. The frequencies of various alleles for the CYP2D6 gene 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.

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