Genetic and phenotypic frequency distribution of CYP2C9, CYP2C19 and CYP2D6 in over 3200 Han Chinese

Abstract Purpose This retrospective study analyzed the polymorphisms and phenotypic frequencies of CYP2C9, CYP2C19 and CYP2D6 in a Han Chinese population. Methods Tests for polymorphisms of CYP2C9 , CYP2C19 and CYP2D6 were performed in over 3000 (3099‐3931) samples using an Illumina HiSeq X Ten sequencer. Following the guidance of the PharmGKB and PharmVar databases, the polymorphisms of CYP2C9 , CYP2C19 and CYP2D6 were transformed into phenotypes, which included ultrarapid metabolizers (UMs), rapid metabolizers (RMs), normal metabolizers (NMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). Results A total of 3122 samples were tested for polymorphisms in CYP2C9 and the overall polymorphism frequency was found to be 8.8%; the phenotypic frequency for CYP2C9 was 91.2% NMs, 8.23% IMs and 0.16%, PMs. The overall polymorphism frequency of CYP2C19 was tested in 3099 samples and found to be 60.1%; the phenotypic frequency for CYP2C19 was 39.9% NMs, with 1.06% RMs, 45.62% IMs and 13.42% PMs. The overall polymorphism frequency of CYP2D6 was tested in 3931 samples and found to be 88.04%; the phenotypic frequency of CYP2D6 was 95.43% NMs, 3.35% IMs and 0.52% PMs. Using 2690 samples, the polymorphisms and phenotypic distributions of CYP2C9, CYP2C19 and CYP2D6 were examined simultaneously. We found that 96.36% of the samples contained mutations while 66.51% corresponded with phenotypic changes. Conclusions Polymorphisms and phenotypic changes of CYP2C9, CYP2C19 and CYP2D6 are relatively frequent in the Han Chinese population. Thus, preemptive pharmacogenetic testing of CYP2C9, CYP2C19 and CYP2D6 should be recommended prior to dosing substrate drugs.