scholarly journals Significant Association of rs2147555 Genetic Polymorphism in the EDNRB Gene with Hirschsprung Disease in Southern Chinese Children

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yi Zheng ◽  
ChaoTing Lan ◽  
Ning Wang ◽  
Xiaogang Xu ◽  
Tuqun Hu ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Significant Risk ◽  
Hirschsprung Disease ◽  
Recessive Model ◽  
Abnormal Development ◽  
Chinese Han ◽  
Southern Chinese ◽  
Ednrb Gene ◽  
Genetic And Environmental Factors

Hirschsprung disease (HSCR) is a human birth defect at the clinical setting, usually characterized by an absent enteric nervous system (ENS) from the distal bowel. The majority of HSCR cases represent a complex disorder resulting from the interaction of multiple genetic and environmental factors. Genetic events have been described to be involved in the abnormal development of the enteric nervous system. Although variants in several genes like RET and EDNRB have been suggested to contribute major risks to HSCR, very little is known about their involvement in the onset of HSCR. Here, we studied a large Chinese Han cohort consisting of 1,470 HSCR patients and 1,473 non-HSCR controls to further test whether there are more variants in EDNRB associated with HSCR. Our results provided the first evidence that rs2147555 in EDNRB confers a significant risk of HSCR in a Chinese Han population for both allelic frequencies ( P = 4.16 × 10 − 3 ; OR = 1.29 ) and genotypic frequencies assuming either a dominant or recessive model ( P = 0.011 and P = 0.027 , respectively). When different subtypes of HSCR cases were analyzed, the association remained significant ( OR = 1.33 , P = 0.003 for short-segment HSCR; OR = 1.34 , P = 0.044 for long segment HSCR).

scholarly journals “Too much guts and not enough brains”: (epi)genetic mechanisms and future therapies of Hirschsprung disease — a review

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Emilie G. Jaroy ◽  
Lourdes Acosta-Jimenez ◽  
Ryo Hotta ◽  
Allan M. Goldstein ◽  
Ragnhild Emblem ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Current Knowledge ◽  
Hirschsprung Disease ◽  
Gut Development ◽  
Dna And Rna ◽  
Expression Of Genes

Abstract Hirschsprung disease is a neurocristopathy, characterized by aganglionosis in the distal bowel. It is caused by failure of the enteric nervous system progenitors to migrate, proliferate, and differentiate in the gut. Development of an enteric nervous system is a tightly regulated process. Both the neural crest cells and the surrounding environment are regulated by different genes, signaling pathways, and morphogens. For this process to be successful, the timing of gene expression is crucial. Hence, alterations in expression of genes specific for the enteric nervous system may contribute to the pathogenesis of Hirschsprung’s disease. Several epigenetic mechanisms contribute to regulate gene expression, such as modifications of DNA and RNA, histone modifications, and microRNAs. Here, we review the current knowledge of epigenetic and epitranscriptomic regulation in the development of the enteric nervous system and its potential significance for the pathogenesis of Hirschsprung’s disease. We also discuss possible future therapies and how targeting epigenetic and epitranscriptomic mechanisms may open new avenues for novel treatment.

Developmental markers of ganglion cells in the enteric nervous system and their application for evaluation of Hirschsprung disease

2014 ◽  
Vol 64 (9) ◽  
pp. 432-442 ◽  
Author(s):  
Hitomi Kawai ◽  
Kaishi Satomi ◽  
Yukio Morishita ◽  
Yoshihiko Murata ◽  
Masato Sugano ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Ganglion Cells ◽  
Hirschsprung Disease

NTF-3, a gene involved in the enteric nervous system development, as a candidate gene for Hirschsprung disease

2008 ◽  
Vol 43 (7) ◽  
pp. 1308-1311 ◽  
Author(s):  
Macarena Ruiz-Ferrer ◽  
Raquel M. Fernandez ◽  
Guillermo Antiñolo ◽  
Manuel Lopez-Alonso ◽  
Salud Borrego
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Candidate Gene ◽  
System Development ◽  
Hirschsprung Disease ◽  
Nervous System Development ◽  
Enteric Nervous System Development

scholarly journals Genetic Variant ofKalirinGene Is Associated with Ischemic Stroke in a Chinese Han Population

2017 ◽  
Vol 2017 ◽  
pp. 1-10
Author(s):  
Hong Li ◽  
Shasha Yu ◽  
Rui Wang ◽  
Zhaoqing Sun ◽  
Xinghu Zhou ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Additive Model ◽  
Recessive Model ◽  
Chinese Han Population ◽  
Dominant Model ◽  
Chinese Han ◽  
Han Population ◽  
Gene Variation ◽  
Pcr Method ◽  
Genetic And Environmental Factors

Introduction.Ischemic stroke is a complex disorder resulting from the interplay of genetic and environmental factors. Previous studies showed that kalirin gene variations were associated with cardiovascular disease. However, the association between this gene and ischemic stroke was unknown. We performed this study to confirm if kalirin gene variation was associated with ischemic stroke.Methods.We enrolled 385 ischemic stroke patients and 362 controls from China. Three SNPs of kalirin gene were genotyped by means of ligase detection reaction-PCR method. Data was processed with SPSS and SHEsis platform.Results.SNP rs7620580 (dominant model: OR = 1.590,p= 0.002 and adjusted OR = 1.662,p= 0.014; additive model: OR = 1.490,p= 0.002 and adjusted OR = 1.636,p= 0.005; recessive model: OR = 2.686,p= 0.039) and SNP rs1708303 (dominant model: OR = 1.523,p= 0.007 and adjusted OR = 1.604,p= 0.028; additive model: OR = 1.438,p= 0.01 and adjusted OR = 1.476,p= 0.039) were associated with ischemic stroke. The GG genotype and G allele of SNP rs7620580 were associated with a risk for ischemic stroke with an adjusted OR of 3.195 and an OR of 1.446, respectively. Haplotype analysis revealed that A–T–G,G-T-A, and A-T-A haplotypes were associated with ischemic stroke.Conclusions.Our results provide evidence that kalirin gene variations were associated with ischemic stroke in the Chinese Han population.

scholarly journals Host Gut Motility and Bacterial Competition Drive Instability in a Model Intestinal Microbiota

2016 ◽  
Author(s):  
Travis J. Wiles ◽  
Matthew L. Jemielita ◽  
Ryan P. Baker ◽  
Brandon H. Schlomann ◽  
Savannah L. Logan ◽  
...  
Keyword(s):  
Nervous System ◽  
Gut Microbiota ◽  
Enteric Nervous System ◽  
Bacterial Species ◽  
Stochastic Perturbation ◽  
Hirschsprung Disease ◽  
Light Sheet ◽  
Mitigation Strategies ◽  
Gut Motility ◽  
Bacterial Competition

AbstractThe gut microbiota is a complex consortium of microorganisms with the ability to influence important aspects of host health and development. Harnessing this ‘microbial organ’ for biomedical applications requires clarifying the degree to which host and bacterial factors act alone or in combination to govern the stability of specific lineages. To address this we combined bacteriological manipulation and light sheet fluorescence microscopy to monitor the dynamics of a defined two-species microbiota within the vertebrate gut. We observed that the interplay between each population and the gut environment produced distinct spatiotemporal patterns. Consequently, one species dominates while the other experiences dramatic collapses that are well fit by a stochastic mathematical model. Modeling revealed that bacterial competition could only partially explain the observed phenomena, suggesting that a host factor is also important in shaping the community. We hypothesized the host determinant to be gut motility, and tested this mechanism by measuring colonization in hosts with enteric nervous system dysfunction due to mutation in the Hirschsprung disease locus ret. In mutant hosts we found reduced gut motility and, confirming our hypothesis, robust coexistence of both bacterial species. This study provides evidence that host-mediated spatial structuring and stochastic perturbation of communities along with bacterial competition drives population dynamics within the gut. In addition, this work highlights the capacity of the enteric nervous system to affect stability of gut microbiota constituents, demonstrating that the ‘gut-brain axis’ is bidirectional. Ultimately, these findings will help inform disease mitigation strategies focused on engineering the intestinal ecosystem.

scholarly journals Copy number variations in candidate genomic regions confirm genetic heterogeneity and parental bias in Hirschsprung disease

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Francesca Lantieri ◽  
Stefania Gimelli ◽  
Chiara Viaggi ◽  
Elissavet Stathaki ◽  
Michela Malacarne ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Genetic Heterogeneity ◽  
Copy Number ◽  
System Development ◽  
Hirschsprung Disease ◽  
Copy Number Variations ◽  
Nervous System Development ◽  
Comparative Genomic ◽  
Genomic Regions

Abstract Background Hirschsprung Disease (HSCR) is a congenital defect of the intestinal innervations characterized by complex inheritance. Many susceptibility genes including RET, the major HSCR gene, and several linked regions and associated loci have been shown to contribute to disease pathogenesis. Nonetheless, a proportion of patients still remains unexplained. Copy Number Variations (CNVs) have already been involved in HSCR, and for this reason we performed Comparative Genomic Hybridization (CGH), using a custom array with high density probes. Results A total of 20 HSCR candidate regions/genes was tested in 55 sporadic patients and four patients with already known chromosomal aberrations. Among 83 calls, 12 variants were experimentally validated, three of which involving the HSCR crucial genes SEMA3A/3D, NRG1, and PHOX2B. Conversely RET involvement in HSCR does not seem to rely on the presence of CNVs while, interestingly, several gains and losses did co-occur with another RET defect, thus confirming that more than one predisposing event is necessary for HSCR to develop. New loci were also shown to be involved, such as ALDH1A2, already found to play a major role in the enteric nervous system. Finally, all the inherited CNVs were of maternal origin. Conclusions Our results confirm a wide genetic heterogeneity in HSCR occurrence and support a role of candidate genes in expression regulation and cell signaling, thus contributing to depict further the molecular complexity of the genomic regions involved in the Enteric Nervous System development. The observed maternal transmission bias for HSCR associated CNVs supports the hypothesis that in females these variants might be more tolerated, requiring additional alterations to develop HSCR disease.

scholarly journals Enteric nervous system development: migration, differentiation, and disease

2013 ◽  
Vol 305 (1) ◽  
pp. G1-G24 ◽  
Author(s):  
Jonathan I. Lake ◽  
Robert O. Heuckeroth
Keyword(s):  
Nervous System ◽  
Neural Crest ◽  
Enteric Nervous System ◽  
System Development ◽  
Hirschsprung Disease ◽  
Nervous System Development ◽  
Receptor Type ◽  
Model Organisms ◽  
Endothelin Receptor ◽  
Type B

The enteric nervous system (ENS) provides the intrinsic innervation of the bowel and is the most neurochemically diverse branch of the peripheral nervous system, consisting of two layers of ganglia and fibers encircling the gastrointestinal tract. The ENS is vital for life and is capable of autonomous regulation of motility and secretion. Developmental studies in model organisms and genetic studies of the most common congenital disease of the ENS, Hirschsprung disease, have provided a detailed understanding of ENS development. The ENS originates in the neural crest, mostly from the vagal levels of the neuraxis, which invades, proliferates, and migrates within the intestinal wall until the entire bowel is colonized with enteric neural crest-derived cells (ENCDCs). After initial migration, the ENS develops further by responding to guidance factors and morphogens that pattern the bowel concentrically, differentiating into glia and neuronal subtypes and wiring together to form a functional nervous system. Molecules controlling this process, including glial cell line-derived neurotrophic factor and its receptor RET, endothelin (ET)-3 and its receptor endothelin receptor type B, and transcription factors such as SOX10 and PHOX2B, are required for ENS development in humans. Important areas of active investigation include mechanisms that guide ENCDC migration, the role and signals downstream of endothelin receptor type B, and control of differentiation, neurochemical coding, and axonal targeting. Recent work also focuses on disease treatment by exploring the natural role of ENS stem cells and investigating potential therapeutic uses. Disease prevention may also be possible by modifying the fetal microenvironment to reduce the penetrance of Hirschsprung disease-causing mutations.

scholarly journals Muscularis macrophage development in the absence of an enteric nervous system

2018 ◽  
Vol 115 (18) ◽  
pp. 4696-4701 ◽  
Author(s):  
Marina Avetisyan ◽  
Julia E. Rood ◽  
Silvia Huerta Lopez ◽  
Rajarshi Sengupta ◽  
Elizabeth Wright-Jin ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Hirschsprung Disease ◽  
Human Colon ◽  
Enteric Neurons ◽  
Local Source ◽  
Normal Numbers ◽  
Adult Mice ◽  
Inflammatory Phenotype ◽  
Cells Of Cajal

The nervous system of the bowel regulates the inflammatory phenotype of tissue resident muscularis macrophages (MM), and in adult mice, enteric neurons are the main local source of colony stimulating factor 1 (CSF1), a protein required for MM survival. Surprisingly, we find that during development MM colonize the bowel before enteric neurons. This calls into question the requirement for neuron-derived CSF1 for MM colonization of the bowel. To determine if intestinal innervation is required for MM development, we analyzed MM of neonatal Ret−/− (Ret KO) mice that have no enteric nervous system in small bowel or colon. We found normal numbers of well-patterned MM in Ret KO bowel. Similarly, the abundance and distribution of MM in aganglionic human colon obtained from Hirschsprung disease patients was normal. We also identify endothelial cells and interstitial cells of Cajal as the main sources of CSF1 in the developing bowel. Additionally, MM from neonatal Ret KOs do not differ from controls in baseline activation status or cytokine-production in response to lipopolysaccharide. Unexpectedly, these data demonstrate that the enteric nervous system is dispensable for MM colonization and patterning in the bowel, and suggest that modulatory interactions between MM and the bowel nervous system are established postnatally.

Sign in / Sign up

Export Citation Format

Share Document