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

Abstract

Objectives To compare CYP2C19 enzyme activity between Swedes and Koreans controlling for the effect of CYP2C19 genotype, sex, oral contraceptive use and smoking habit.Methods CYP2C19 activity was determined in 185 healthy Swedish and 150 Korean subjects as omeprazole/5-hydroxyomeprazole ratio (metabolic ratio; MR) using high-performance liquid chromatography. Genotyping was performed by PCR using Taqman assay.Results As expected, a higher incidence of poor metabolizers (PM) was found in Koreans (14%) compared to 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 effect of smoking was observed. ConclusionsWe 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.

Evaluation of Predictive Cyp2C19 Genotyping Assays Relative to Measured Phenotype in a South African Cohort

“…In the study by Ramsjö et al [38], it was reported that the cut-off in Koreans was as high as -3.04, while it was a low -0.86 17 in a Swedish cohort. The cut-off value separating the PM and IM phenotypes in this study was -1.152, which is within the range of cut-off values previously reported.…”

“…Previous studies have reported CYP2C19 phenotypic cut-off values, separating PMs from IMs/EMs, to range between log MR (5OH/OME) -0.6 and -3.04 [32,38,39]. In the study by Ramsjö et al [38], it was reported that the cut-off in Koreans was as high as -3.04, while it was a low -0.86 17 in a Swedish cohort.…”

Cilostazol to Overcome High On-Treatment Platelet Reactivity in Korean Patients Treated With Clopidogrel and Calcium-Channel Blocker

“…Further support for this observation comes from C EDITORIAL a novel in vitro pharmacodynamic assay, which demonstrated that CYP3A4/5 isoenzymes play a significant role in both hepatic oxidation steps of clopidogrel. 11 Among subjects homozygous for CYP2C19*1, Koreans displayed significantly lower CYP2C19 enzyme activity than Swedes (P<0.000001), 12 which may imply that CYP3A4/5 enzyme activity plays a more important role in clopidogrel metabolism among Koreans. The addition of cilostazol in PCI-treated patients has been shown to reduce major cardiovascular events such as mortality, myocardial infarction and stent thrombosis.…”

Influence of CYP2C19*2 and *3 loss-of-function alleles on the pharmacodynamic effects of standard- and high-dose clopidogrel in East Asians undergoing percutaneous coronary intervention: the results of the ACCEL-DOUBLE-2N3 study

“…For example, Korean subjects carrying the CYP2C19*1/*1 gene had higher a metabolic ratio than Swedish subjects (1.48 vs. 0.58; P < 0.000001), indicating lower CYP2C19 activity in Koreans [6]. However, the contribution of the CYP2C19 LoF allele to platelet reactivity appears similar during clopidogrel treatment.…”

“…East Asians with the same genotype as Caucasians have shown lower CYP2C19 activity [3,6]. For example, Korean subjects carrying the CYP2C19*1/*1 gene had higher a metabolic ratio than Swedish subjects (1.48 vs. 0.58; P < 0.000001), indicating lower CYP2C19 activity in Koreans [6].…”