高原世居藏族和移居汉族人群 CYP2C19 基因多态性比较分析

Comparative analysis of CYP2C19 gene polymorphism between Tibetan and migrant Han populations in high altitude

目的比较细胞色素P450(cytochrome P450,CYP450)的同工酶CYP2C19在高原世居藏族和移居汉族人群中的不同基因型及等位基因分布特点,为高原地区抗血小板药物氯吡格雷使用前是否进行基因检测提供依据。方法选取2021年1月至12月在西藏自治区人民医院就诊的藏、汉人群(分别为200例、120例),采用荧光定量PCR检测藏、汉人群CYP2C19基因多态性,并比较高原地区藏、汉人群基因型和代谢型的分布特点。结果CYP2C19在高原地区藏、汉人群中*1/*1、*1/*2、*1/*3、*2/*2、*2/*3、*3/*3基因型分布频率分别为49%、36.5%、6.5%、7.5%、0.5%、0%和47.5%、39%、4%、6%、2.5%、1%,等位基因*1、*2、*3分布频率分别为70.5%、26%、3.5%和69.1%、26.7%、4.2%,两组间基因型和等位基因分布差异无统计学意义(P>0.05);快代谢(EM,*1/*1)、中间代谢(IM,*1/*2、*1/*3)、慢代谢(PM,*2/*2、*2/*3、*3/*3)分布频率分别为49%、43%、8%和47.5%、42.5%、10%,两组间差异亦无统计学意义(P>0.05)。结论高原世居藏族人群中CYP2C19基因代谢型和基因型与移居汉族人群比较无差异,且中间代谢型及慢代谢型人群占比超过50%。在高原地区藏、汉人群中使用氯吡格雷之前有必要进行CYP2C19基因型检测,并根据基因型结果调整用药。

Objective To compare the genotype and allele distribution of cytochrome P450(CYP450)isoenzyme CYP2C19 between native Tibetans and Han migrants at high altitude,and provide evidence for the necessity of genetic testing before the clinical use of clopidogrel,an antiplatelet drug,in high altitude area.Methods A total of 200 Tibetan and 120 Han Chinese hospitalized in the People′s Hospital of Tibet Autonomous Region from January 2021 to December 2021 were selected to detect CYP2C19 gene polymorphism by fluorescence PCR,and compare the distribution characteristics of genotypes and metabolites in Tibetan and Han population in high-altitude areas.Results The genotype frequency distributions of*1/*1,*1/*2,*1/*3,*2/*2,*2/*3,and*3/*3 of CYP2C19 in Tibetan and Han populations of high altitude area were 49%,36.5%,6.5%,7.5%,0.5%,0%and 47.5%,39%,4%,6%,2.5%,1%,respectively.The distribution frequencies of alleles*1,*2,and*3 were 70.5%,26%,3.5%and 69.1%,26.7%,4.2%,respectively.There was no significant difference in genotype and allele distribution between the two groups(P>0.05).The distribution frequencies of fast metabolism(EM,*1/*1),intermediate metabolism(IM,*1/*2,*1/*3)and slow metabolism(PM,*2/*2,*2/*3 and*3/*3)were 49%,43%,8%and 47.5%,42.5%,10%,respectively.There was no significant difference between the two groups(P>0.05).Conclusion There are no significant differences in the metabolites and genotypes of CYP2C19 gene between Tibetan and migrant Han populations.The results of both groups show that intermediate metabolic type and slow metabolic type account for more than 50%of the population.Therefore,it is necessary to conduct CYP2C19 genotype detection before using clopidogrel in Tibetan and Han Chinese populations in plateau areas,and adjust medication according to the genotype results.