CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking

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.