基于microRNA研究孕前移居高原对子代先天性心脏病的影响

Study on the Effect of Pre-pregnancy on Congenital Heart Disease in Offspring Migration to High Altitude Based on MicroRNA

目的:基于microRNA探讨孕前移居高原对子代发生先天性心脏病的影响。方法:收集2018年1月1日—2019年12月31日西藏拉萨阜康妇产儿童医院样本,将平原移居高原孕妇生育的先天性心脏病患儿作为病例组,以平原移居高原孕妇生育的健康儿童作为对照组。抽取两组血浆并进行microRNA表达谱分析和RT-PCR验证,用MiRanda和TargetScan两个数据库预测差异microRNA的靶基因,并对靶基因进行GO Enrichment分析和Pathway Enrichment分析,筛选出与先天性心脏病相关microRNA。结果:病例组与对照组比较,上调microRNA有21个,下调microRNA有24个。RT-PCR验证结果与芯片检测结果一致。对差异显著基因进行生物信息学分析后,筛选出靶基因PDK4和PON1受上调的miR-107和miR-26a-5p的调节。结论:miR-107和miR-26a-5p与孕前移居高原后子代发生先天性心脏病相关。

Objective:This studyis aimed to investigate the effect of pre-pregnancy migration to high altitude on the occurrence of congenital heart disease in offspring based on microRNA.Methods:Samples were collected from the Fukang Maternity and Children's Hospital in Lhasa,Tibet.The case group were the children with congenital heart disease bom by pregnant women who migrated to high altitude from the plain,and the control group were the normal children bom by pregnant women who migrated to high altitude from the plain.The two groups of plasma were extracted and analyzedby microRNA microarray and RT-PCR validation were performed.MiRanda and TargetScan databases were used to predict the target genes of differential microRNAs,and GO Enrichment analysis and Pathway Enrichment analysis were performed on the target genes to screen out microRNAs related to congenital heart disease.Results:There were 21 up-regulated microRNAs and 24 down-regulated microRNAs in the case group compared with the control group.The RT-PCR verification results are consistent with the chip detection results.After the bioinformatics analysis of significant different genes,the target genes PDK4 and PON1 were selected to be regulated by up-regulated miR-107 and miR-26a-5p.Conclusions:MiR-107 and miR-26a-5p are associated with congenital heart disease in offspring after migrating to high altitude before pregnancy.