17q21 locus and ORMDL3: An increased risk for childhood asthma Review uri icon

Overview

MeSH Major

  • Asthma
  • Chromosomes, Human, Pair 17
  • Genetic Variation
  • Membrane Proteins

abstract

  • Genetic variations in the 17q21 locus are strongly associated with childhood nonallergic asthma. Expression of the 17q21 genes, orosomucoid like 3 (ORMDL3) and gasdermin B (GSMDB), is affected by these disease-associated variants. However, until recently, no functional connection of the protein products coded by these genes with asthma was known. Lately, it has been identified that ORMDL3 function has been related to various cellular processes that could be relevant for the pathogenesis of asthma. This includes dysregulation of the unfolded protein response (UPR) associated with airway remodeling and also an effect of ORMDL3-dysregulated sphingolipid synthesis on bronchial hyperreactivity. These findings are crucial for a better understanding of the mechanism of childhood asthma and may lead to asthma therapeutics that target pathways previously not thought to be related to this common pediatric respiratory disease. Furthermore, this may validate the unbiased genome-wide association study (GWAS) approach for complex diseases such as asthma, to better define pathomechanisms and drug targets.

publication date

  • January 2014

Research

keywords

  • Review

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/pr.2013.186

PubMed ID

  • 24165737

Additional Document Info

start page

  • 165

end page

  • 70

volume

  • 75

number

  • 1-2