Gene-environmental interactions and the severity of asthma exacerbations
The severity of Rhinovirus-triggered asthma exacerbations is influenced by gene-environment interactions between virus and host genetic background.
Rhinovirus is one of the main cause of morbidity among children with asthma. However, there is marked inter-individual variation in the susceptibility to and severity of rhinovirus-triggered asthma exacerbation, ranging from mild symptoms to life-threatening episodes. Knowing the basis of this clinical variation is essential in order to to understand the biological mechanisms that pre-dispose some children to severe asthma exacerbations. A genome-wide association study (GWAS) identified a novel nonsynonymous coding single nucleotide polymorphism (SNP) -rs6967330- at the cadherin-related family member 3 (CDHR3) locus, which strongly associated with recurrent episodes of severe asthma exacerbations in children. CDHR3 is a transmembrane protein acting as a functional Rhinovirus C receptor in vitro. Therefore, the severity of Rhinovirus-triggered asthma exacerbations is influenced by gene-environment interactions between virus and host genetic background. A subsequent study found that the same polymorphism was associated with the detection of Rhinovirus C in the nasal aspirates of children with moderate to severe respiratory infections, but not with the detection of other viruses. This suggests that the variation at the CDHR3 allele confers an increased risk of severe asthma exacerbation through an increased cell surface expression of CDHR3, resulting in increased rhinovirus C binding and replication. Moreover, the finding raise the possibility that the CDHR3 risk allele increases the frequency of viral-induced wheezing episodes during infancy, which together with atopy, is strongly associated with the inception of asthma later in life. More precise characterizing of the genetic background will improve shaping of childhood asthma phenotypes, risk stratification and treatment.
Kantor DB, et al. Gene-environment Interactions Associated with the Severity of Acute Asthma Exacerbation in Children. Am J Respir Crit Care Med. 2017 Nov 21. doi: 10.1164/rccm.201711-2166ED. [Epub ahead of print]