Association of Neuregulin 1 rs7835688 G &gt; C, rs16879552 T &gt; C and rs2439302 G &gt; C Polymorphisms with Susceptibility to Non-Syndromic Hirschsprung’s Disease

Hosseini-Jangjou, Seyed Hamed; Dastgheib, Seyed Alireza; Aflatoonian, Majid; Amooee, Abdolhamid; Bahrami, Reza; Salehi, Elham; Sadeghizadeh‐Yazdi, Jalal; Neámatzadeh, Hossein

doi:10.1080/15513815.2019.1692113

Cited by 2 publications

(1 citation statement)

References 26 publications

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“…It encodes a signal membrane protein which effects as a key regulator in the progression of various systems such as the nervous system, circulation system, and so on ( 25 , 26 ). Additionally, NRG1 polymorphisms have been shown to be associated with schizophrenia, Alzheimer's disease, Hirschsprung's disease, TC, and other carcinoma development and metastasis ( 27 – 29 ). rs2439302 has been reported to influence NRG1 gene expression in the GTEx data, and Huiling et al reported that the risk allele [G] is associated with the upregulation of NRG1; further, a DNA silencing of 32 kb containing the risk [G] allele of rs2439302 was revealed to harbor multiple candidate functional variants ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

Investigating the Association Between rs2439302 Polymorphism and Thyroid Cancer: A Systematic Review and Meta-Analysis

Guo

Zhang

et al. 2022

Front. Surg.

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Background and AimsThe extent of surgical treatment for most patients with thyroid cancer (TC) remains controversial and varies widely. As an emerging technology, genetic testing facilitates tumor typing and disease progression monitoring and is expected to influence the choice of surgical approach for patients with TC. Recent genome-wide association studies (GWASs) have identified that rs2439302 (8p12) variants near NRG1 are associated with TC risk; however, the results remain inconclusive. Therefore, we aimed to perform a meta-analysis to clarify the association between rs2439302 variants and the risk of TC.MethodsWe search eligible studies using Pubmed, Scopus, Embase, Web of Science, and Cochrane library by July 2021. We analyzed the pooled OR and the corresponding 95% confidence interval (95% CI) of the included studies and then conducted subgroup analysis according to the ethnicity. We also performed a sensitivity analysis to validate the findings.ResultsThis meta-analysis finally included 7 studies involving 6,090 cases and 14,461 controls. Results showed that the G allele of the rs2439302 polymorphism was a significant risk factor of TC in Allele (G/C), Dominant (GG+GC/CC), Recessive (GG/GC+CC), Homozygote (GG/CC), Heterozygote (GC/CC) models, with pooled ORs of 1.38 (95%CI, 1.31–1.45), 1.51 (95%CI, 1.41–1.62), 1.52 (95%CI, 1.40–1.66), 1.90 (95%CI, 1.71–2.10), and 1.40 (95%CI, 1.30–1.51), respectively. The subgroup analysis showed that rs2439302 polymorphism was associated with higher TC risk in different ethnicities with OR > 1. The sensitivity analysis exhibited that the results were stable by omitting any included studies.ConclusionsThe study revealed that rs2439302 variants were associated with higher TC risk and may have a major influence on the choice of operative approach for patients with TC.

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Section: Discussionmentioning

confidence: 99%

Investigating the Association Between rs2439302 Polymorphism and Thyroid Cancer: A Systematic Review and Meta-Analysis

Guo

Zhang

et al. 2022

Front. Surg.

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The interplay of common genetic variants NRG1 rs2439302 and RET rs2435357 increases the risk of developing Hirschsprung’s disease

Chi,

Li,

Cao

et al. 2023

Front. Cell Dev. Biol.

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Introduction: As a congenital and genetically related disease, many single nucleotide polymorphisms (SNPs) have been reported to be associated with the risk of HSCR. Our previous research showed that SNP rs2439302 (NRG1) interacted with rs2435357 (RET) to increase the risk of HSCR development. However, the underlying molecular mechanism is still not well understood.Methods: SNP rs2439302 (NRG1) and rs2435357 (RET) were genotyped in 470 HSCR cases. The expression of NRG1 and RET was investigated in the colon of HSCR patients. Knockdown of the NRG1 and RET homologs was performed in zebrafish to investigate their synergistic effect on ENS development. The effect of SNP rs2439302 and rs2435357 polymorphism on neuron proliferation, migration, and differentiation were investigated in SHSY-5Y cells and IPSCs.Results: Significant downregulation of NRG1 and RET expression was noticed in the aganglionic segment of HSCR patients and SHSY-5Y cells with rs2439302 GG/rs2435357 TT genotype. NRG1 and RET double mutants caused the most severe reduction in enteric neuron numbers than NRG1 single mutant or RET single mutant in the hindgut of zebrafish. SHSY-5Y cells and IPSCs with rs2439302 GG/rs2435357 TT genotype exhibited a decreased proliferative, migration, and differentiative capacity. CTCF showed a considerably higher binding ability to SNP rs2439302 CC than GG. NRG1 reduction caused a further decrease in SOX10 expression via the PI3K/Akt pathway, which regulates RET expression by directly binding to rs2435357.Discussion: SNP rs2439302 (NRG1) GG increases the risk of developing HSCR by affecting the binding of transcription factor CTCF and interacting with rs2435357 (RET) to regulate RET expression via the PI3K/Akt/SOX10 pathway.

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Association of Neuregulin 1 rs7835688 G > C, rs16879552 T > C and rs2439302 G > C Polymorphisms with Susceptibility to Non-Syndromic Hirschsprung’s Disease

Cited by 2 publications

References 26 publications

Investigating the Association Between rs2439302 Polymorphism and Thyroid Cancer: A Systematic Review and Meta-Analysis

Investigating the Association Between rs2439302 Polymorphism and Thyroid Cancer: A Systematic Review and Meta-Analysis

The interplay of common genetic variants NRG1 rs2439302 and RET rs2435357 increases the risk of developing Hirschsprung’s disease

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