影响青蒿素类药物代谢的相关基因位点突变在新疆哈萨克族人群中的分布  

Distribution of gene mutation sites affecting artemisinin metabolism in the Kazak population in Xinjiang

作　　者：周雪红[1] 徐薇 刁彤[2] 王丽[2] 李凯 ZHOU Xue-hong;XU Wei;DIAO Tong;WANG Li;LI Kai(Altay People's Hospital,Altay,Xinjiang 836500,China;General Hospital of Xinjiang Military Region,Urumqi,Xinjiang 830000,China)

机构地区：[1]新疆阿勒泰地区人民医院,新疆阿勒泰836500 [2]新疆军区总医院,新疆乌鲁木齐830000

出　　处：《中国热带医学》2023年第4期435-438,共4页China Tropical Medicine

摘　　要：目的检测影响青蒿素类药物代谢相关的CYP2A6^(*)2、CYP2A6^(*)10、CYP2A6^(*)17、CYP2B6^(*)4、CYP2B6^(*)6、CYP2B6^(*)18等位点的频率在新疆地区哈萨克族人群中的分布,探究新疆地区哈萨克族人群对于青蒿素类药物的药物遗传学背景,为新疆地区人群基于青蒿素药物的疟疾治疗和预防提供临床决策。方法选取CYP2A6^(*)2、CYP2A6^(*)10、CYP2A6^(*)17、CYP2B6^(*)4、CYP2B6^(*)6、CYP2B6^(*)18共6个位点进行测序实验。收集新疆哈萨克族人群全血样本330人份,提取全血DNA基因组后,利用多重PCR技术及高通量测序技术进行分型,分析其分布频率,采用哈迪-温伯格定律对相应位点的基因型分布进行检验。结果本研究中各单核苷酸多态性(single nucleotide polymorphism,SNP)位点测序结果均符合哈迪温伯格平衡定律(P>0.05),不同性别人群的SNP位点分布差异无统计学意义(P>0.05)。CYP2A6^(*)2、CYP2A6^(*)10、CYP2A6^(*)17、CYP2B6^(*)4、CYP2B6^(*)6、CYP2B6^(*)18测序成功的样本数分别为326份、319份、328份、318份、322份、328份,在新疆哈萨克族人群中变异等位基因的频率分别为0.61%、0、0、30.97%、22.98%、0。结论新疆地区哈萨克族人群中存在影响青蒿素类疟疾预防及治疗药物代谢的相关位点突变,在使用青蒿素类药物时,应进一步探索观察用药效果与个体药物遗传学背景的关系。Objective To detect the distribution of CYP2A6^(*)2,CYP2A6^(*)10,CYP2A6^(*)17,CYP2B6^(*)4,CYP2B6^(*)6,and CYP2B6^(*)18 loci affecting the metabolism of artemisinins in Kazak population in Xinjiang.To explore the pharmacogenetic background of the Kazak population in Xinjiang for artemisinin drugs and provide clinical decision support for the treatment and prevention of malaria based on artemisinin drugs.Methods Six SNPs including CYP2A6^(*)2,CYP2A6^(*)10,CYP2A6^(*)17,CYP2B6^(*)4,CYP2B6^(*)6,and CYP2B6^(*)18 were selected for the sequencing experiment.330 whole blood samples were collected from the Kazak population in Xinjiang.After extracting the whole blood DNA genome,multiplex PCR and high-throughput sequencing were used for genotyping.The allele frequencies were analyzed using the Hardy-Weinberg equilibrium.Results In this study all SNPs follow the Hardy-Weinberg equilibrium(P>0.05),there was no significant difference in the distribution of SNPs between different genders(P>0.05).The number of successfully sequenced samples of CYP2A6^(*)2,CYP2A6^(*)10,CYP2A6^(*)17,CYP2B6^(*)4,CYP2B6^(*)6,and CYP2B6^(*)18 were 326,319,328,318,322 and 328 respectively.The frequencies of variant alleles of CYP2A6^(*)2,CYP2A6^(*)10,CYP2A6^(*)17,CYP2B6^(*)4,CYP2B6^(*)6,and CYP2B6^(*)18 in Kazak population are:0.61%,0%,0%,30.97%,22.98%,0%.Conclusions Mutation alleles affecting the metabolism of artemisinins exist in the Kazak population in Xinjiang.When using artemisinins,the relationship between the drug effect and individual pharmacogenetic background should be further explored.

关 键 词：疟疾 青蒿素 细胞色素P450家族 基因多态性 

分 类 号：R531.1[医药卫生—内科学]