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

Li He; Shaojun Chen; Jingao Li; Xiaoxue Xie; Lihua Huang; Yun Kuang; Kangwei Xu; Wanxia Huang; Yanling Zhao; Guoping Yang; Chengxian Guo

doi:10.1111/1440-1681.13357

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

Clin Exp Pharmacol Physiol. 2020 Oct;47(10):1659-1663. doi: 10.1111/1440-1681.13357. Epub 2020 Jun 16.

Authors

Li He¹, Shaojun Chen², Jingao Li³, Xiaoxue Xie⁴, Lihua Huang⁵, Yun Kuang⁶, Kangwei Xu⁷, Wanxia Huang⁷, Yanling Zhao⁶, Guoping Yang⁶, Chengxian Guo⁶

Affiliations

¹ Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China.
² Department of Oncology, Fourth Affiliated Hospital, Guangxi Medical University, Liuzhou, China.
³ Department of Radiotherapy, Jiangxi Tumor Hospital, Nanchang, China.
⁴ Department of Radiotherapy, Hunan Provincial Tumor Hospital and Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, China.
⁵ Center for Medical Experiments, The Third Xiangya Hospital, Central South University, Changsha, China.
⁶ Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.
⁷ Hunan Normal University School of Medicine, Changsha, China.

PMID: 32469422
DOI: 10.1111/1440-1681.13357

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.

Keywords: CYP2C19; CYP2C9; CYP2D6; phenotype; polymorphism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

China
Cytochrome P-450 CYP2C19 / genetics*
Cytochrome P-450 CYP2D6 / genetics*
Humans
Phenotype*

Substances

CYP2C19 protein, human
Cytochrome P-450 CYP2C19
Cytochrome P-450 CYP2D6