中国内地藏族、蒙古族、维吾尔族和汉族人群 CYP3A4、CYP3A5、CYP3A7 和 GSTP1 基因多态性的等位基因和基因型频率。

Allele and genotype frequencies of CYP3A4, CYP3A5, CYP3A7, and GSTP1 gene polymorphisms among mainland Tibetan, Mongolian, Uyghur, and Han Chinese populations.

机构信息

Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Pharmacology, Basic Medical School, Peking University, Beijing, China.

出版信息

Clin Exp Pharmacol Physiol. 2022 Feb;49(2):219-227. doi: 10.1111/1440-1681.13604. Epub 2021 Nov 2.

DOI:10.1111/1440-1681.13604

PMID:34689350

Abstract

Over 50% prescribed drugs are metabolised by cytochrome P450 3A (CYP3A) and glutathione S-transferase pi (GSTP1) adds a glutathione to the oxidative products by CYP3A, which increases the hydrophilic property of metabolites and facilitates the excretion. Single nucleotide polymorphisms (SNPs) of CYP3A and GSTP1 show a diverse allele and genotype frequencies distribution among the world populations. The present study aimed to investigate the genotype and allele frequency distribution patterns of CYP3A4, CYP3A5, CYP3A7 and GSTP1 polymorphisms among healthy participants in mainland Tibetan, Mongolian, Uyghur, and Han Chinese populations. Blood samples were collected from 842 unrelated healthy subjects (323 Tibetan, 134 Mongolian, 162 Uyghur, and 223 Han) for genotyping analysis. Variant allele frequencies of CYP3A4 rs2242480, CYP3A5 rs776746, CYP3A7 rs2257401, and GSTP1 Ile105Val were observed in Han (0.253, 0.686, 0.312 and 0.188), Tibetan (0.186, 0.819, 0.192 and 0.173), Mongolian (0.198, 0.784, 0.228 and 0.235) and Uyghur (0.179, 0.858, 0.182 and 0.250) respectively. The allele frequency of CYP3A7*1C in Uyghur (0.019) was higher than that in Tibetan (0.002, p < 0.01). There was a strong linkage disequilibrium between CYP3A4 rs2242480, CYP3A5 rs776746, and CYP3A7 rs2257401 among the four ethnic groups. The results might be useful for the precise medication in the Chinese populations.

摘要

超过 50%的处方药物是由细胞色素 P450 3A（CYP3A）和谷胱甘肽 S-转移酶 pi（GSTP1）代谢的，CYP3A 将谷胱甘肽添加到氧化产物中，增加了代谢物的亲水性，并促进了排泄。CYP3A 和 GSTP1 的单核苷酸多态性（SNP）在世界人群中的等位基因和基因型频率分布存在多样性。本研究旨在调查 CYP3A4、CYP3A5、CYP3A7 和 GSTP1 多态性在中国大陆藏族、蒙古族、维吾尔族和汉族健康参与者中的基因型和等位基因频率分布模式。从 842 名无关的健康个体（323 名藏族、134 名蒙古族、162 名维吾尔族和 223 名汉族）中采集血样进行基因分型分析。在汉族（0.253、0.686、0.312 和 0.188）、藏族（0.186、0.819、0.192 和 0.173）、蒙古族（0.198、0.784、0.228 和 0.235）和维吾尔族（0.179、0.858、0.182 和 0.250）中观察到 CYP3A4 rs2242480、CYP3A5 rs776746、CYP3A7 rs2257401 和 GSTP1 Ile105Val 的变异等位基因频率。维吾尔族中 CYP3A7*1C 的等位基因频率（0.019）高于藏族（0.002，p<0.01）。在四个民族中，CYP3A4 rs2242480、CYP3A5 rs776746 和 CYP3A7 rs2257401 之间存在强连锁不平衡。研究结果可能对中国人群的精准用药有帮助。