Ormdl3 -gen

ORMDL3, is a gene located on chromosome 17q21. The gene is expressed in airway epithelia. It encodes the highly conserved protein group ORMDL3, which acts as transmembrane receptor proteins in the endoplasmic reticulum.

Polymorphisms of the gene occur significantly more frequently in children suffering from bronchial asthma. They thus represent a risk factor for bronchial asthma, as was found in a study involving 2,643 children.

The role of the ORMDL3 protein complex is still largely unexplained. In knock-out mice in which the ORMDL3 gene is switched off, cytokines on the surface of eosinophilic granulocytes are suppressed, which have the ability of these cells to migrate and initiate inflammation in the airways. Furthermore, the ORMDL3 protein complex influences metalloproteases (MMP-9, ADAM-8) and cytokines (CCL-20, Il-8, CXCL 10/11) involved in inflammatory processes.

1. Miller M et al (2012) ORMDL3 is an inducible lung epithelial gene regulating metalloproteases, chemokines, OAS, and ATF6. Proc Natl Acad Sci U S A 109:16648-16653.
2. Schedel M et al (2015) Polymorphisms related to ORMDL3 are associated with asthma susceptibility, alterations in transcriptional regulation of ORMDL3, and changes in TH2 cytokine levels. J Allergy Clin Immunol 136:893-903.
3. Zhao CN et al (2015) The Association of GSDMB and ORMDL3 Gene Polymorphisms With Asthma: A Meta-Analysis. Allergy Asthma Immunol Res 7:175-185.