TY - JOUR
T1 - Ethnic differences in CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) genotypes in Japanese and Israeli populations
AU - Nakai, Kenji
AU - Habano, Wataru
AU - Nakai, Keiko
AU - Fukushima, Noriko
AU - Suwabe, Akira
AU - Moriya, Shogo
AU - Osano, Kaoru
AU - Gurwitz, David
N1 - Funding Information:
This study was supported by a Grant-in-aid for Scientific Research (No. 15590768) in Japan Society for the Promotion of Science, the Test of Fostering Potential of Japan Science and Technology Corporation, and Open Research Translational Research Center Project, Advanced Medical Science Center, Iwate Medical University.
PY - 2005/11/19
Y1 - 2005/11/19
N2 - 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.
AB - 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.
KW - Adverse drug reactions
KW - CYP2C9
KW - DNA array
KW - Ethnic differences
KW - Genotyping
KW - Pharmacogenetics
KW - Single nucleotide polymorphism
UR - http://www.scopus.com/inward/record.url?scp=27344445176&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2005.04.049
DO - 10.1016/j.lfs.2005.04.049
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C2 - 16111713
AN - SCOPUS:27344445176
SN - 0024-3205
VL - 78
SP - 107
EP - 111
JO - Life Sciences
JF - Life Sciences
IS - 1
ER -