摘要
目的基于MiniSeq基因测序技术对先天性巨结肠症患者NRG1、NRG3和SOX10基因多个位点单核苷酸多态性进行检测,探讨基因多态性与先天性巨结肠症发病的相关性。方法选择本院在2019年2月到2023年2月期间确诊为先天性巨结肠症患儿74例作为病例组,并将同期83例健康儿童纳入对照组。基于MiniSeq基因测序技术对两组研究对象NRG1、NRG3和SOX10基因7个位点单核苷酸多态性进行检测,探讨不同基因型与先天性巨结肠症发病的相关性。通过Logistic回归分析确定先天性巨结肠症发病的独立危险因素,依据筛选出的因素构建预测先天性巨结肠症发病风险的列线图模型,并验证此模型。结果病例组和对照组患者的7个单核苷酸多态性位点中,rs10748842、rs139884、rs16879552、rs10883866及rs6584400位点各基因型在两组间的分布频率差异均不显著(P>0.05);病例组患者NRG1基因rs2439302位点CG和GG基因型人数显著高于对照组,并且rs7835688位点GC和CC基因型人数显著高于对照组(P<0.05);多因素分析表明,性别、母孕期主/被动吸烟、母亲接触有毒物质、rs2439302-G和rs7835688-C等位基因是影响先天性巨结肠症发病的危险因素,利用这些因素构建的列线图预测模型,内部验证前后曲线下面积分别为0.837、0.841,灵敏度分别为86.5%和89.2%,特异度分别为77.1%、78.3%,准确性良好。结论NRG1是先天性巨结肠症的易感基因,rs2439302-G和rs7835688-C为先天性巨结肠症发病的风险等位基因,而rs16879552、rs6584400、rs139884、rs10748842和rs10883866与先天性巨结肠症发病无明显相关性;基于性别、母孕期主/被动吸烟、母亲接触有毒物质、rs2439302-G和rs7835688-C构建的列线图模型对先天性巨结肠症发病风险有较好的预测效果。
Objective Based on MiniSeq gene sequencing technology,multiple loci single nucleotide polymorphisms of NRG1,NRG3 and SOX10 genes in patients with Hirschsprung’s disease(HD)were detected,and their correlation with the incidence of HD was discussed.Methods 74 children diagnosed with HD from February 2019 to February 2023 in our hospital were selected as the case group,and 83 healthy children were included in the control group during the same period.Single nucleotide polymorphism(SNP)of NRG1,NRG3 and SOX10 genes in the two groups was detected based on MiniSeq gene sequencing technology to explore the correlation between different genotypes and HD.Independent risk factors for HD were screened by Logistic regression analysis,and a nomogram model for predicting HD was constructed according to the screened factors,and the model was then verified.Results There was no significant difference in the distribution frequency of rs10748842,rs139884,rs16879552,rs10883866 and rs6584400 genotypes between the case and control groups(P>0.05).The number of patients with CG and GG genotypes at rs2439302 of NRG1 gene in the case group was significantly higher than that in the control group,and the number of patients with GC and CC genotypes at rs7835688 was significantly higher than that in the control group(P<0.05).Multivariate analysis showed that gender,maternal active/passive smoking during pregnancy,maternal exposure to toxic substances,rs2439302-G and rs7835688-C alleles were independent influencing factors for the incidence of HD.A nomogram prediction model was constructed based on the selected risk factors.The area under the curve before and after internal verification was 0.837 and 0.841,the sensitivity was 86.5%and 89.2%,the specificity was 77.1%and 78.3%,respectively,and the accuracy was good.Conclusion NRG1 is a susceptibility gene for HD,rs2439302-G and rs7835688-C are risk alleles for HD,while rs16879552,rs139884,rs10748842,rs10883866 and rs6584400 had no significant correlation with HD;The nomogram model based on gender,maternal active/passive smoking during pregnancy,maternal exposure to toxic substances,and rs2439302-G and rs7835688-C had a good predictive effect on the risk of HD.
作者
王意
刘应松
马达
Wang Yi;Liu Yingsong;Ma Da(Department of Pediatric Surgery,Dongguan Eighth People’s Hospital,Dongguan Children’s Hospital,Dongguan Guangdong 523320,China)
出处
《遵义医科大学学报》
2023年第12期1176-1184,1189,共10页
Journal of Zunyi Medical University
基金
东莞市社会科技发展(重点)项目(NO:201950715028167)。
