Childhood asthma is associated with mutations and gene expression differences of ORMDL genes that can interact

@article{Toncheva2015ChildhoodAI,
  title={Childhood asthma is associated with mutations and gene expression differences of ORMDL genes that can interact},
  author={Antoaneta A. Toncheva and Daniel P. Potaczek and Michaela Schedel and Soeren W. Gersting and Sven Michel and Natalie Krajnov and Vincent D Gaertner and J. M. Klingbeil and Thomas Illig and Andr{\'e} Franke and C. Winkler and Jens M. Hohlfeld and Christian Vogelberg and Andrea von Berg and Albrecht Bufe and Andrea Heinzmann and Otto Laub and Ernst Th. Rietschel and Burkhard Simma and Jon Genuneit and Ania Carolina Muntau and Michael Kabesch},
  journal={Allergy},
  year={2015},
  volume={70},
  pages={1288 - 1299}
}
Genomewide association studies identified ORMDL3 as a plausible asthma candidate gene. ORMDL proteins regulate sphingolipid metabolism and ceramide homeostasis and participate in lymphocyte activation and eosinophil recruitment. Strong sequence homology between the three ORMDL genes and ORMDL protein conservation among different species suggest that they may have shared functions. We hypothesized that if single nucleotide polymorphisms (SNPs) in ORMDL3 alter its gene expression and play a role… 
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29 Citations
Background Citations
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Results Citations
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29 Citations

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Citation Type

Ormdl3 and Allergic Asthma: from Physiology to Pathology.
Airway reactivity and sphingolipids—implications for childhood asthma
TLDR
How sphingolipid mediators sphingosine-1-phosphate (S1P) and ceramide have been shown to be important signaling molecules for airway hyperreactivity, mast cell activation, and inflammation is highlighted.
Human β-Defensin 2 Mutations Are Associated With Asthma and Atopy in Children and Its Application Prevents Atopic Asthma in a Mouse Model
TLDR
It is found that prophylactic oral administration of hBD-2 significantly curbed lung resistance and pulmonary inflammation in the authors' HDM mouse model, suggesting that h BD-2 could be involved in the protective farm effect and may be an excellent candidate to confer protection against asthma development.
An Integrative Transcriptomic and Metabolomic Study of Lung Function in Children With Asthma
The role of ORMDL proteins, guardians of cellular sphingolipids, in asthma
A family of widely expressed ORM‐like (ORMDL) proteins has been recently linked to asthma in genomewide association studies in humans and extensively explored in in vivo studies in mice. ORMDL…
Precision Medicine in Childhood Asthma: Omic Studies of Treatment Response
TLDR
These studies have identified novel associations of genetic markers, epigenetic modifications, metabolites, bacteria, and molecular mechanisms involved in asthma treatment response that will allow establishing molecular biomarkers that could be integrated with clinical information to improve the management of children with asthma.
Epigenetic Mechanisms in Allergy Development and Prevention.
TLDR
Considering that allergic disorders possess multiple clinical (phenotypes) and mechanistic (endotypes) forms, targeted, stratified treatment strategies based on detailed clinical and molecular diagnostics are required, since conventional diagnostic or therapeutic approaches do not suffice, this gap could possibly be filled out by epigenetic approaches.
The IL‐4 rs2070874 polymorphism may be associated with the severity of recurrent viral‐induced wheeze
TLDR
It is shown that childhood recurrent wheezing and consequently asthma corresponds to various phenotypes, and genetic variants of asthma candidate genes to the phenotypes of early onset wheazing are linked.
The puzzle of immune phenotypes of childhood asthma
TLDR
This review summarizes recent key findings on the complex mechanisms of the development and manifestation of childhood asthma as well as the development of new biomarkers and the discovery of new immunological molecules.
Epigenetics and allergy: from basic mechanisms to clinical applications.
TLDR
The potential of epigenetic changes for various clinical applications is shown: as diagnostic tools, to assess tolerance following immunotherapy or possibly predict the success of therapy at an early time point and new technological advances such as epigenome editing and DNAzymes will allow targeted alterations of the epigenome in the future and provide novel therapeutic tools.
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References

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TLDR
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TLDR
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