Ethnic differences in CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) genotypes in Japanese and Israeli populations

Kenji Nakai*, Wataru Habano, Keiko Nakai*, Noriko Fukushima, Akira Suwabe, Shogo Moriya, Kaoru Osano, David Gurwitz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

CYP2C9 is a major P450 2C enzyme, which hydroxylates about 16% of drugs that are in current clinical use and contributes to the metabolism of a number of clinically important substrate drugs such as warfarin. Ethnic differences in the genetic variation of CYP2C9 have been reported, and might be related to the frequencies of adverse reactions to drugs metabolized by CYP2C9 in different ethnic groups. In the present study, ethnic differences in the CYP2C9*2 and CYP2C9*3 allele distribution in Japanese and Israeli populations were evaluated using a newly developed oligonucleotide based DNA array (OligoArrayR). The population studied consisted of 147 Japanese and 388 Israeli donors (100 Ashkenazi Jews, 99 Yemenite Jews, 100 Moroccan Jews and 89 Libyan Jews). The CYP2C9*2 [Arg144Cys (416 C > T), exon 3] and CYP2C9*3 [Ile359Leu (1061 A > C), exon 7] genotypes were determined using an OligoArrayR. The accuracy of genotyping by the OligoArrayR was verified by the fluorescent dye-terminator cycle sequencing method. A Hardy-Weinberg test indicated equilibrium (χ2 < 3.84 is Hardy-Weinberg) in all populations. The CYP2C9*2 genotype (CC/CT + TT) was absent in Japanese (1/0) (OR 0.02), and its frequency was significant in Libyan Jews (0.697/0.303) (OR 2.13; 95% CI 1.07-4.24) compared with Ashkenazi Jews (0.83/0.17), Yemenite Jews (0.899/0.101), and Moroccan Jews (0.81/0.19). The frequencies of CYP2C9*3 genotype (AA/AC + CC) was significantly lower in Japanese (0.986/0.014) (OR 0.08), and was higher in Libyan Jews (0.652/0.348) (OR 3.03; 95% CI 1.5-6.1) and Moroccan Jews (0.77/0.23) (OR 1.69; 95% CI 0.62-3.48) compared with those in Ashkenazi Jews (0.85/0.15) and Yemenite Jews (0.849/0.151). Thus, the CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) variants were rare in the Japanese population, and showed different frequencies in the four Jewish ethnic groups examined.

Original languageEnglish
Pages (from-to)107-111
Number of pages5
JournalLife Sciences
Volume78
Issue number1
DOIs
StatePublished - 19 Nov 2005

Funding

FundersFunder number
Advanced Medical Science Center
Fostering Potential of Japan Science and Technology Corporation
Grant-in-aid for Scientific Research15590768
Iwate Medical University
Japan Society for the Promotion of Science

    Keywords

    • Adverse drug reactions
    • CYP2C9
    • DNA array
    • Ethnic differences
    • Genotyping
    • Pharmacogenetics
    • Single nucleotide polymorphism

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