重庆地区儿童CYP450基因多态性
| 作者: |
1何小丽,
2褚京乐,
2何燕
1 重庆市永川区儿童医院医务科，重庆 402160 2 重庆市永川区妇幼保健院药剂科，重庆 402160 |
| 通讯: |
何燕
Email: din7536@163.com |
| DOI: | 10.3978/j.issn.2095-6959.2021.12.007 |
| 基金: | 社会事业与民生保障项目(YCSTC，2018CC0205)。 |
摘要
目的：了解重庆地区儿童细胞色素氧化酶450(CYP450)单核苷酸多态性，为指导儿童用药提供支持。方法：使用PCR法检测400例儿童中CYP2D6 (100C>T)、CYP2C9 (1075A>C)、CYP2C19 (681G>A)、CYP3A4 (878T>C)、CYP3A5 (6986A>G)基因亚型和等位基因的频率，计算各基因亚型的代谢表型分布。结果：纳入重庆地区400例儿童，其中男221例，女179例，年龄0.5~16.0(5.5±4.6)岁。各个基因亚型分布符合Hardy Weinberg遗传平衡定律。野生型纯合子占比较高的位点为CYP2C9 (1075A>C)和CYP3A4 (878T>C)，而杂合子占比较高的位点为CYP2D6 (100C>T)。CYP3A4 (878T>C)的突变纯合子未检出。以快代谢型基因亚型为主的基因亚型为CYP2D6、CYP2C9、CYP3A4和CYP3A5，而以中间/慢代谢型为主的基因亚型为CYP2C19。结论：CYP2C19和CYP3A5儿童存在较大比例慢代谢人群，在临床诊疗过程中需要根据代谢表型指导用药。
关键词：
细胞色素氧化酶450；单核苷酸多态性；基因频率；代谢表型
CYP450 gene polymorphism of children in Chongqing
CorrespondingAuthor: HE Yan Email: din7536@163.com
DOI: 10.3978/j.issn.2095-6959.2021.12.007
Foundation: This work was supported by the Social Undertakings and Livelihood Security Project, China (YCSTC, 2018cc0205).
Abstract
Objective: To investigate the single nucleotide polymorphism (SNP) of cytochrome P450 (CYP450) in children in Chongqing area, and to provide support for the guidance of drug use in children. Methods: The frequency of CYP2D6 (100C>T), CYP2C9 (1075A>C), CYP2C19 (681G>A), CYP3A4 (878T>C), CYP3A5 (6986A>G) gene subtypes and alleles in 400 children were detected by PCR, and the metabolic phenotypic distribution of each gene subtype was calculated. Results: This study included 400 children in Chongqing area, including 221 male children and 179 female children, aged 0.5–16 (5.5±4.6) years. The distribution of each gene subtype conformed to Hardy Weinberg’s law of genetic equilibrium. CYP2C9 (1075A>C) and CYP3A4 (878T>C) occupied a higher proportion of wild type homozygous loci. CYP2D6 (100C>T) was the most heterozygous locus. The mutant homozygous of CYP3A4 (878T>C) was not detected. The fast metabolic subtypes were CYP2D6, CYP2C9, CYP3A4 and CYP3A5, while the intermediate/slow metabolic subtype was CYP2C19. Conclusion: There is a large proportion of CYP2C19 and CYP3A5 children with slow metabolism, and drug use should be guided according to the metabolic phenotype in the clinical treatment process.
Keywords：
cytochrome P450; single nucleotide polymorphism; gene frequency; metabolic phenotype