法洛四联症与NOTCH1和JAG1基因3′非编码区变异的相关性研究  

Study on correlation between tetralogy of Fallot and variation of 3′UTR of NOTCH1 and JAG1 genes

作　　者：杨小芳[1] 崔芬芬 李元敏[1] 周文君[1] 党国琴 胡源[1] 路宁[1] YANG Xiaofang;CUI Fenfen;LI Yuanmin;ZHOU Wenjun;DANG Guoqin;HU Yuan;LU Ning(Department of Cardiovascular Surgery,First Hospital of Lanzhou University,Lanzhou,Gansu 730000,China)

机构地区：[1]兰州大学第一医院心血管外科,兰州730000

出　　处：《重庆医学》2021年第10期1715-1720,共6页Chongqing medicine

基　　金：甘肃省自然科学基金项目(18JR3RA346)。

摘　　要：目的探讨法洛四联症(TOF)与NOTCH1和JAG1基因3′非编码区(3′UTR)变异的相关性,为TOF患者临床诊断提供遗传依据。方法采用民族-病例-对照的研究方法,收集20例汉族TOF患者及14例回族TOF患者,并分别以20名汉族及20名回族健康体检者为对照组,筛选出TOF患者在两个民族人群中,NOTCH1和JAG1基因3′UTR存在的变异。通过PCR技术,结合DNA序列测序,测定、验证、确定样本人群中这些变异位点;进一步运用TargetScan、PicTar和microRNA.org等软件对变异位点可能结合miRNA进行分析,推测其和TOF发生、发展的相关性。结果检测出TOF患者NOTCH1基因3′UTR存在3个单核苷酸多态性(SNP),JAG1基因3′UTR存在6个SNP位点。9个SNP位点在4组对象中的分布频数存在差异,但差异无统计学意义(P>0.05)。其中JAG1基因3′UTR rs542746042位点在汉族对照组与汉族病例组之间的分布,差异有统计学意义(P<0.05)。预测结果显示,JAG1基因3′UTR有差异的SNP位点(486delT)可与miRNA结合。结论NOTCH1和JAG1基因3′UTR的核苷酸变异可能与TOF的发生相关。Objective To explore the correlation between tetralogy of Fallot(TOF)and the variation of 3′UTR of NOTCH1 and JAG1 genes to provide the genetic basis for the diagnosis of the patients with TOF.Methods The ethnology case-control study method was adopted,20 Han cases of TOF and 14 Hui cases of TOF were collected,and 20 Han and 20 Hui subjects undergoing healthy physical examination served as the control group.The existing variations in 3′UTR of NOTCH1 and JAG1 genes in two ethnic groups was screened out.These variation sites in the sample population were detected,verified and confirmed through the PCR technology,combined with DNA sequence sequencing;then the softwares such as TargetScan,PicTar and microRNA.org were used to analyze the possible combination of mutation sites with miRNA,and speculate their correlation with the occurrence and development of TOF.Results Three single nucleotide polymorphisms(SNPs)were detected in the 3′UTR of NOTCH1 gene and six SNPs in the JAG13′UTR of TOF patients.The distribution frequency of 9 SNP loci in the 4 groups was different,but the difference was not statistically significant(P>0.5).The distribution of 3′UTR rs542746042 loci in JAG1 gene had statistical difference between the Han control group and Han case group(P<0.05).The predicted results showed that the SNP site(486delT)with different JAG1 gene 3′UTR could bind to miRNA.Conclusion The nucleotide variation of NOTCH1 and JAG1 gene 3′UTR may be related to the occurrence of TOF.

关 键 词：法洛四联症 NOTCH1基因 JAG1基因 3′非编码区 单核苷酸多态性 

分 类 号：R541.1[医药卫生—心血管疾病]