Frequencies of Clinically Important CYP2C19 and CYP2D6 Alleles across East Asian populations

Abstract

Cytochrome P450 2C19 (CYP2C19) and 2D6 (CYP2D6) are vital drug metabolic enzymes involved in the metabolism of many important prescription drugs. Importantly, CYP2C19 and CYP2D6 genes are highly polymorphic and harbor a plethora of genetic variants that change enzyme activity and consequently result in individual differences in drug metabolism, response and toxicity. While CYP2C19 and CYP2D6 alleles are highly population-specific, we overviewed distribution of 6 clinically important CYP2C19 (CYP2C19*2, *3 and *17) and CYP2D6 (CYP2D6*5, *10 and duplications) alleles within East Asian populations (including Chinese, South Korean and Japanese) as well as Chinese subethnic populations based on 30 original studies and 25,948 healthy individuals. We found that the frequency of CYP2C19*3 shows an obvious West-to-East gradient, ranging from 4.3% in Han Chinese to 12% in Japanese. Within the Chinese subethnic populations, we observed that the frequencies of CYP2C19*2 were graded similarly from West to East China and Hui population harbors strikingly high CYP2C19*2 frequency (42.7%) among all studied populations. In addition, there is a very clear South-to-North gradient of CYP2C19*3 frequencies across China, ranging from 1.5% in Li to 8% in Kazakh. Patterns of CYP2D6 allele distributions are difficult to conclude due to the lack of reported frequency data. In summary, we described frequencies of important CYP2C19 and CYP2D6 alleles in East Asian populations and Chinese ethnic populations, which can serve as important information for the guidance of East Asian population-specific genotyping strategies as well as dose adjustment in drug prescriptions.