CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking
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To compare CYP2C19 enzyme activity between Swedes and Koreans controlling for the effect of CYP2C19 genotype, sex, oral contraceptive use, and smoking habits.
CYP2C19 activity was determined in 185 healthy Swedish and 150 Korean subjects as the omeprazole/5-hydroxyomeprazole ratio (metabolic ratio; MR) using high-performance liquid chromatography. Genotyping was performed by PCR using Taqman assay.
As expected, a higher incidence of poor metabolizers (PM) was found in Koreans (14%) compared with Swedes (3.8%) and the frequency of the CYP2C19*17 allele was very low in Koreans (0.3%). Among subjects homozygous for CYP2C19*1, Koreans displayed significantly lower CYP2C19 enzyme activity than Swedes (p < 0.000001). Interestingly, in Koreans a pronounced gender difference was apparent: females (n = 24) had significantly lower MR than males (n = 30; p < 0.0001), but such a gender difference was not seen among Swedes. Swedish OC users had a higher MR than non-users (p < 0.00001), whereas OC was only used by one Korean. No effects of smoking were observed.
We find specific gender-dependent effects of CYP2C19 activity in Koreans, but not in Swedes. Controlling for the effect of genotype and sex, Koreans display lower CYP2C19 activity than Swedes. The genetic, epigenetic or environmental basis for this difference remains to be identified.
KeywordsCYP2C19 Omeprazole Gender Korean Swedes
The study was financially supported by the Swedish Research Council, Medicine, 3902 and the Swedish Capio Forskningsstiftelse.
- 13.Ishizaki T, Sohn DR, Kobayashi K, Chiba K, Lee KH, Shin SG, Andersson T, Regardh CG, Lou YC, Zhang Y et al (1994) Interethnic differences in omeprazole metabolism in the two S-mephenytoin hydroxylation phenotypes studied in Caucasians and Orientals. Ther Drug Monit 16(2):214–215CrossRefPubMedGoogle Scholar
- 17.Sim SC, Risinger C, Dahl ML, Aklillu E, Christensen M, Bertilsson L, Ingelman-Sundberg M (2006) A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 79(1):103–113CrossRefPubMedGoogle Scholar
- 25.Kim JI, Ju YS, Park H, Kim S, Lee S, Yi JH, Mudge J, Miller NA, Hong D, Bell CJ, Kim HS, Chung IS, Lee WC, Lee JS, Seo SH, Yun JY, Woo HN, Lee H, Suh D, Kim HJ, Yavartanoo M, Kwak M, Zheng Y, Lee MK, Kim JY, Gokcumen O, Mills RE, Zaranek AW, Thakuria J, Wu X, Kim RW, Huntley JJ, Luo S, Schroth GP, Wu TD, Kim H, Yang KS, Park WY, Church GM, Lee C, Kingsmore SF, Seo JS (2009) A highly annotated whole-genome sequence of a Korean individual. Nature 460(7258):1011–1015PubMedGoogle Scholar
- 26.Tamminga WJ, Wemer J, Oosterhuis B, Weiling J, Wilffert B, de Leij LF, de Zeeuw RA, Jonkman JH (1999) CYP2D6 and CYP2C19 activity in a large population of Dutch healthy volunteers: indications for oral contraceptive-related gender differences. Eur J Clin Pharmacol 55(3):177–184CrossRefPubMedGoogle Scholar