Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Oncology, Fourth Affiliated Hospital, Guangxi Medical University, Liuzhou, China.
Clin Exp Pharmacol Physiol. 2020 Oct;47(10):1659-1663. doi: 10.1111/1440-1681.13357. Epub 2020 Jun 16.
This retrospective study analyzed the polymorphisms and phenotypic frequencies of CYP2C9, CYP2C19 and CYP2D6 in a Han Chinese population.
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).
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.
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.
本回顾性研究分析了汉族人群中 CYP2C9、CYP2C19 和 CYP2D6 的多态性和表型频率。
使用 Illumina HiSeq X Ten 测序仪对超过 3000 个（3099-3931 个）样本进行 CYP2C9、CYP2C19 和 CYP2D6 的多态性检测。根据 PharmGKB 和 PharmVar 数据库的指导，将 CYP2C9、CYP2C19 和 CYP2D6 的多态性转化为表型，包括超快代谢者（UMs）、快速代谢者（RMs）、正常代谢者（NMs）、中间代谢者（IMs）和慢代谢者（PMs）。
共检测了 3122 个 CYP2C9 样本的多态性，总体多态性频率为 8.8%；CYP2C9 的表型频率为 91.2%为 NMs，8.23%为 IMs，0.16%为 PMs。共检测了 3099 个 CYP2C19 样本的总体多态性频率，发现其为 60.1%；CYP2C19 的表型频率为 39.9%为 NMs，1.06%为 RMs，45.62%为 IMs，13.42%为 PMs。共检测了 3931 个 CYP2D6 样本的总体多态性频率，发现其为 88.04%；CYP2D6 的表型频率为 95.43%为 NMs，3.35%为 IMs，0.52%为 PMs。使用 2690 个样本，同时检测 CYP2C9、CYP2C19 和 CYP2D6 的多态性和表型分布。结果发现，96.36%的样本存在突变，66.51%的样本与表型变化相对应。
汉族人群 CYP2C9、CYP2C19 和 CYP2D6 的多态性和表型变化较为频繁。因此，在给予底物药物前，建议对 CYP2C9、CYP2C19 和 CYP2D6 进行预先遗传药理学检测。
