[1]傅润熹,王阳,蔡威.DLL3基因遗传多态性与先天性巨结肠易感性的相关性分析[J].临床小儿外科杂志,2023,22(04):351-355.[doi:10.3760/cma.j.cn101785-202203030-010]
　Fu Runxi,Wang Yang,Cai Wei.Association study of delta-ligand 3 (DLL3) gene with Hirschsprung’s disease susceptibility[J].Journal of Clinical Pediatric Surgery,2023,22(04):351-355.[doi:10.3760/cma.j.cn101785-202203030-010]
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DLL3基因遗传多态性与先天性巨结肠易感性的相关性分析

《临床小儿外科杂志》[ISSN:1671-6353/CN:43-1380/R] 卷: 第22卷 期数: 2023年04 页码: 351-355 栏目: 论著 出版日期: 2023-04-28
Title:
Association study of delta-ligand 3 (DLL3) gene with Hirschsprung’s disease susceptibility
作者:
傅润熹;  王阳;  蔡威
上海交通大学医学院附属新华医院小儿外科 上海市儿科医学研究所 上海市小儿消化与营养重点实验室, 上海 200092
Author(s):
Fu Runxi;  Wang Yang;  Cai Wei
Department of Pediatric Surgery, Affiliated Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University;Shanghai Institute for Pediatric Researches, Shanghai Key Laboratory of Pediatric Gastroenterology & Nutrition, Shanghai 200092, China Fu Runxi and Wang Yang contributed equally to this work
关键词:
Hirschsprung病; 病因学; 基因
Keywords:
Hirschsprung Disease; Etiology; Genes
DOI:
10.3760/cma.j.cn101785-202203030-010
摘要:
目的 探讨DLL3基因多态性与先天性巨结肠(hirschsprung’s disease,HSCR)易感性之间的关系。方法 采用病例对照研究方法,选取2009—2012年上海交通大学医学院附属新华医院小儿外科收治的104例HSCR病例(HSCR组)和151例就诊于小儿外科而无慢性便秘病史的对照病例(对照组)作为研究对象。采用MassARRAY的方法检测DLL3基因5个单核苷酸多态性(single nucleotide polymorphism,SNP)位点的多态性分布,统计分析不同等位基因、基因型以及单倍型与HSCR易感性之间的相关性。结果 HSCR组5个SNP位点rs3786951、rs958728、rs2304214、rs3212276、rs10412931基因型、等位基因频率与对照组比较,差异无统计学意义(P＞0.05)。rs3786951-rs958728-rs2304214-rs3212276-rs10412931组遗传标记具有强LD(linkage disequilibrium)(D’＞0.7)。HSCR组GGTAC单倍型携带频率为11.9%,高于对照组的6.4%,该单倍型与HSCR的发生显著相关(rs3786951-rs958728-rs2304214-rs3212276-rs10412931,P=0.049,OR=1.87,95%CI 0.99~3.50)。结论 DLL3基因中,由5个SNP位点rs3786951、rs958728、rs2304214、rs3212276、rs10412931构成的GGTAC单倍型与HSCR易感性相关,单个SNP位点与HSCR之间无显著相关性。
Abstract:
Objective To explore the association between single nucleotide polymorphisms (SNPs) in delta-ligand 3(DLL3) gene and examine the susceptibility to Hirschsprung’s Disease (HSCR).Methods For this case-control study,104 cases of HSCR were recruited and 151 cases without a history of chronic constipation as control group.MassARRAY was performed for examining the five SNPs’ polymorphism in DLL3.The relationship between the risk of HSCR and different genotypes,allelic genes and haplotypes were compared.Results There were no statistical differences of 5 SNPs rs3786951/rs958728/rs2304214/rs3212276/rs10412931 genotype and allelic gene frequencies between HSCR and control group (P>0.05).Estimation of linkage disequilibrium for each pair of SNPs revealed strong linkage disequilibrium (D’＞0.7) for one group of markers (rs3786951-rs958728-rs2304214-rs3212276-rs10412931).The frequency of GGTAC haplotypes was higher in HSCR group than that in control group (11.9% vs.6.4%).Significant differences existed in susceptibility to HSCR (rs3786951-rs958728-rs2304214-rs3212276-rs10412931,P=0.049,OR=1.87,95%CI 0.99-3.50).Conclusion The GGTAC haplotypes of 5SNPs rs3786951,rs958728,rs2304214,rs3212276 and rs10412931 in DLL3 gene are associated with susceptibility to HSCR.However,no significant correlation exists between single SNP and HSCR.

参考文献/References:

[1] 陈宏坤,张大森.先天性巨结肠患者血清miR-223与炎性因子水平及其临床意义研究[J].临床小儿外科杂志,2021,20(4):359-364.DOI:10.12260/lcxewkzz.2021.04.011. Chen HK,Zhang DS.Clinical significance of serum levels of miR-223 and inflammatory factors in children with Hirschsprung’s disease[J].J Clin Ped Sur,2021,20(4):359-364.DOI:10.12260/lcxewkzz.2021.04.011.
[2] Nagy N,Goldstein AM.Enteric nervous system development:a crest cell’s journey from neural tube to colon[J].Semin Cell Dev Biol,2017,66:94-106.DOI:10.1016/j.semcdb.2017.01.006.
[3] 张彦,夏慧敏.先天性巨结肠的遗传发病机制及前瞻性队列研究进展[J].临床小儿外科杂志,2018,7(2):90-93.DOI:10.3969/j.issn.1671-6353.2018.02.003. Zhang Y,Xia HM.Hirschsprung disease:research advances of genetic pathogenesis and prospective cohort study[J].J Clin Ped Sur,2018,17(2):90-93.DOI:10.3969/j.issn.1671-6353.2018.02.003.
[4] Liu MT,Huang WS,Guo YJ,et al.CAR NK-92 cells targeting DLL3 kill effectively small cell lung cancer cells in vitro and in vivo[J].J Leukoc Biol,2022,112(4):901-911.DOI:10.1002/JLB.5MA0122-467R.
[5] Ngan ESW,Garcia-Barceló MM,Yip BHK,et al.Hedgehog/Notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans[J].J Clin Invest,2011,121(9):3467-3478.DOI:10.1172/JCI43737.
[6] Wang Y,Wang J,Pan WH,et al.Common genetic variations in Patched1(PTCH1) gene and risk of Hirschsprung disease in the Han Chinese population[J].PLoS One,2013,8(9):e75407.DOI:10.1371/journal.pone.0075407.
[7] Kuil LE,MacKenzie KC,Tang CS,et al.Size matters:large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development[J].PLoS Genet,2021,17(8):e1009698.DOI:10.1371/journal.pgen.1009698.
[8] Stavely R,Bhave S,Ho WLN,et al.Enteric mesenchymal cells support the growth of postnatal enteric neural stem cells[J].Stem Cells,2021,39(9):1236-1252.DOI:10.1002/stem.3388.
[9] 童玲,臧婧羽,袁小建,等.RhoA/ROCK信号通路在先天性巨结肠病变肠段的变化研究[J].临床小儿外科杂志,2018,17(3):226-230.DOI:10.3969/j.issn.1671-6353.2018.03.014. Tong L,Zang JY,Yuan XJ,et al.Variation of RhoA/ROCK signaling pathway in colon of Hirschsprung’s disease[J].J Clin Ped Sur,2018,17(3):226-230.DOI:10.3969/j.issn.1671-6353.2018.03.014.
[10] Karim A,Tang CSM,Tam PKH.The emerging genetic landscape of Hirschsprung disease and its potential clinical applications[J].Front Pediatr,2021,9:638093.DOI:10.3389/fped.2021.638093.
[11] Jiang Q,Wang Y,Li Q,et al.Sequence characterization of RET in 117 Chinese Hirschsprung disease families identifies a large burden of de novo and parental mosaic mutations[J].Orphanet J Rare Dis,2019,14(1):237.DOI:10.1186/s13023-019-1194-2.
[12] Kapoor A,Nandakumar P,Auer DR,et al.Multiple,independent,common variants at RET,SEMA3 and NRG1 gut enhancers specify Hirschsprung disease risk in European ancestry subjects[J].J Pediatr Surg,2021,56(12):2286-2294.DOI:10.1016/j.jpedsurg.2021.04.010.
[13] Okamoto M,Uesaka T,Ito K,et al.Increased RET activity coupled with a reduction in the RET gene dosage causes intestinal aganglionosis in mice[J].eNeuro,2021,8(3):ENEURO.0534-ENEU20.2021.DOI:10.1523/ENEURO.0534-20.2021.
[14] Soret R,Schneider S,Bernas G,et al.Glial cell-derived neurotrophic factor induces enteric neurogenesis and improves colon structure and function in mouse models of Hirschsprung disease[J].Gastroenterology,2020,159(5):1824-1838.e17.DOI:10.1053/j.gastro.2020.07.018.
[15] Chatterjee S,Karasaki KM,Fries LE,et al.A multi-enhancer RET regulatory code is disrupted in Hirschsprung disease[J].Genome Res,2021,31(12):2199-2208.DOI:10.1101/gr.275667.121.
[16] Chatterjee S,Chakravarti A.A gene regulatory network explains RET-EDNRB epistasis in Hirschsprung disease[J].Hum Mol Genet,2019,28(18):3137-3147.DOI:10.1093/hmg/ddz149.
[17] McCallum S,Obata Y,Fourli E,et al.Enteric glia as a source of neural progenitors in adult zebrafish[J].Elife,2020,9:e56086.DOI:10.7554/eLife.56086.
[18] Pawolski V,Schmidt MHH.Neuron-glia interaction in the developing and adult enteric nervous system[J].Cells,2020,10(1):47.DOI:10.3390/cells10010047.
[19] Jia HM,Zhang KR,Chen QJ,et al.Down-regulation of Notch-1/Jagged-2 in human colon tissues from Hirschsprung disease patients[J].Int J Colorectal Dis,2012,27(1):37-41.DOI:10.1007/s00384-011-1295-4.
[20] Faure S,McKey J,Sagnol S,et al.Enteric neural crest cells regulate vertebrate stomach patterning and differentiation[J].Development,2015,142(2):331-342.DOI:10.1242/dev.118422.
[21] Theocharatos S,Wilkinson DJ,Darling S,et al.Regulation of progenitor cell proliferation and neuronal differentiation in enteric nervous system neurospheres[J].PLoS One,2013,8(1):e54809.DOI:10.1371/journal.pone.0054809.
[22] Liu JAJ,Ngan ESW.Hedgehog and Notch signaling in enteric nervous system development[J].Neurosignals,2014,22(1):1-13.DOI:10.1159/000356305.
[23] Noor H,Whittaker S,McDonald KL.DLL3 expression and methylation are associated with lower-grade glioma immune microenvironment and prognosis[J].Genomics,2022,114(2):110289.DOI:10.1016/j.ygeno.2022.110289.

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备注/Memo

收稿日期:2022-3-11。
基金项目:上海市自然科学基金(22ZR1451500);上海市小儿消化与营养重点实验室(17DZ2272000)
通讯作者:蔡威,Email:caiw204@sjtu.edu.cn

更新日期/Last Update: 1900-01-01