Association of Rs2435357 and Rs1800858 Polymorphisms in Ret Proto-Oncogene With Hirschsprung Disease: Systematic Review and Meta-Analysis

Amooee, Abdolhamid; Lookzadeh, Mohamad Hosein; Mirjalili, Seyed Reza; Miresmaeili, Seyed Mohsen; Aghili, Kazem; Zare-Shehneh, Masoud; Neámatzadeh, Hossein

doi:10.1590/0102-672020190001e1448

Cited by 5 publications

(5 citation statements)

References 38 publications

(38 reference statements)

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“…The OVOL2 gene is involved in epithelial development and differentiation, and in humans OVOL2 has been associated with corneal dystrophy (Chung et al, 2019). The RET gene encodes a protein that is involved in cell signaling essential for normal development of several kinds of nerve cells, and genetic variants in this gene have been associated with Hirschsprung disease, a birth defect characterized by absence of ganglion nerve cells in the bowel (Amooee et al, 2019). It is interesting that the un‐penalized estimate of the VC for the gene SHH

false(σ^{2} = 0.153 false)

was the third largest, yet in the penalized models this VC was shrunk to zero.…”

Section: Resultsmentioning

confidence: 99%

Penalized variance components for association of multiple genes with traits

Schaid

Sinnwell

Larson

2020

Genetic Epidemiology

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Variance component models have gained popularity for genetic analyses, driven by their flexibility to simultaneously analyze multiple genetic variants in a gene by kernel statistics, and their ability to account for population stratification via genomic relationship matrices. For exploratory analyses with modest sample sizes and a potentially large number of variance components, it can be challenging to use standard maximum‐likelihood or restricted maximum‐likelihood methods to estimate variance components, because these iterative methods often fail to converge when likelihood surfaces are fairly flat, and standard‐likelihood ratio statistical tests are not adequate. To overcome these limitations, we developed a penalized‐likelihood model, whereby the penalty function follows the popular elastic‐net approach, applying both L1 and L2 penalties to the variance components. By simulations, we demonstrate the potential gain in power by using both L1 and L2 penalties, and results from our simulations suggest that assigning 80% of the penalty parameter to the L1 penalty and 20% to the L2 penalty provides a reasonable balance between false‐positive and false‐negative results. Larger sample size improves the properties of our methods, at the cost of longer computation time. Application of our methods to a study of the influence of DNA methylation on levels of cortisol in reaction to stress testing shows how our method can be used to prioritize findings for further functional studies.

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false(σ^{2} = 0.153 false)

was the third largest, yet in the penalized models this VC was shrunk to zero.…”

Section: Resultsmentioning

confidence: 99%

Penalized variance components for association of multiple genes with traits

Schaid

Sinnwell

Larson

2020

Genetic Epidemiology

View full text Add to dashboard Cite

show abstract

“…These mechanisms are in harmonizing with two other enhancers in RET : one binding TF GATA2 and the other binding TF RARB ( 22 ). In addition, recent meta-analysis studies showed that besides RET rs2435357, other variants in RET also increased HSCR risk, including rs1800858, rs1800861, and rs10900297 ( 23 , 24 ). Further study is necessary to investigate the somatic mosaicism of those three RET variants to confirm our findings.…”

Section: Discussionmentioning

confidence: 99%

Is There Any Mosaicism in REarranged During Transfection Variant in Hirschsprung Disease’s Patients?

et al. 2022

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BackgroundHirschsprung disease (HSCR) is a heterogeneous genetic disease characterized by the absence of ganglion cells in the intestinal tract. The REarranged during Transfection (RET) is the most responsible gene for its pathogenesis. RET’s somatic mosaicisms have been reported for HSCR; however, they are still under-recognized. Therefore, we determined the frequency of somatic mutation of RET rs2435357 in HSCR patients at our institution.MethodsWe performed RET rs2435357 genotyping from 73 HSCR formalin-fixed and paraffin-embedded (FFPE) rectal and 60 non-HSCR controls using the PCR-RFLP method. Subsequently, we compared those frequencies of genotypes for RET rs2435357 with our previous genotyping data from 93 HSCR blood specimens.ResultsThe frequencies of genotypes for RET rs2435357 in HSCR paraffin-embedded rectal were CC 0, CT 11 (15%), and TT 62 (85%), whereas their frequencies in HSCR blood samples were CC 4 (4.3%), CT 22 (23.7%), and TT 67 (72%). Those frequencies differences almost reached a significant level (p = 0.06). Moreover, the frequency of RET rs2435357 risk allele (T) was significantly higher in HSCR patients (135/146, 92.5%) than controls (46/120, 38.3%) (p = 3.4 × 10–22), with an odds ratio of 19.74 (95% confidence interval = 9.65–40.41).ConclusionOur study suggests somatic mosaicism in HSCR patients. These findings further imply the complexity of the pathogenesis of HSCR. Moreover, our study confirms the RET rs2435357 as a significant genetic risk factor for HSCR patients.

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“…Following the inclusion exclusion criteria 78 studies were excluded to case reports, review, previous meta-analyses, and other polymorphisms of MTHFR gene or lack of the relevant data. Finally, a total of 20 case-control studies from eleven independent papers (Kimura et al, 2001;Sanyal et al, 2004;Moore et al, 2004Moore et al, , 2007Lin et al, 2004;Karagas et al, 2005;Cai et al, 2009;Wang et al, 2009;Rouissi et al, 2009;Chung et al, 2010;Safarinejad et al, 2011;Amooee et al, 2019) were selected. The main characteristics of each study identified are listed in Table 1.…”

Section: Discussionmentioning

confidence: 99%

“…Keywords: Bladder cancer-urinary neoplasms-folate-MTHFR-polymorphism-meta-analysis REVIEW Associations of MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) Polymorphisms with Susceptibility to Bladder Cancer: A Systematic Review and Meta-Analysis respectively (Bouffioux, 1984). Bladder cancer is one of the most expensive cancer to care for from diagnosis to death due to the frequent procedures required for this malignancy monitoring and treatment (Andreassen et al, 2016).…”

Section: Introductionmentioning

confidence: 99%