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Reduced CDHR3 expression in children wheezing with rhinovirus
Katarina Stenberg Hammar1,2,3, Katarzyna Niespodziana4, Marianne van Hage5
1Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Insights
Rhinovirus (RV) wheezing in children is linked to asthma. This study found reduced CDHR3 mRNA levels in wheezing children, suggesting a potential biomarker for identifying severe cases.
Area of Science:
- Pediatric respiratory infections
- Molecular genetics
- Asthma research
Background:
- Rhinovirus (RV)-induced wheezing in young children is associated with later asthma risk.
- Cadherin-related family member 3 (CDHR3) is the RV-C receptor; the rs6967330 genetic variant affects RV-C binding and replication.
- The genetic variant rs6967330 and CDHR3 mRNA expression in children with acute wheezing were investigated.
Purpose of the Study:
- To examine the association of rs6967330 genotypes and CDHR3 mRNA expression with rhinovirus presence and symptoms in children with acute wheezing.
- To compare these factors between wheezing children and age-matched healthy controls.
Main Methods:
- Genotyping of the rs6967330 G>A variant in 216 children.
- Measurement of CDHR3 mRNA expression in peripheral blood leukocytes of 69 children with RV-induced wheezing and healthy controls using TaqMan assays.
- Comparison of genotypes and mRNA levels between acute wheezing, follow-up visits, and controls.
Main Results:
- The risk allele rs6967330-A was significantly more common in the wheezing group (P < .001).
- Children with acute wheezing exhibited reduced CDHR3 mRNA levels compared to controls (P = .001).
- Genotypes AA/AG for rs6967330 showed the most significant changes in CDHR3 expression between acute and follow-up visits (P < .04).
Conclusions:
- Reduced CDHR3 mRNA levels in preschool children with RV-induced wheezing may increase airway permeability and vulnerability.
- CDHR3 mRNA levels could serve as a biomarker to identify a more severe phenotype of wheezing in preschool children.
- This finding contributes to understanding the genetic and molecular basis of rhinovirus-induced wheezing and asthma risk.
Background:
Rhinovirus-induced wheezing in young children has been associated with increased asthma risk at school age. Recently, the transmembrane protein cadherin-related family member 3 (CDHR3) was identified as the RV-C receptor and the genetic variant rs6967330 (p.Cys529Tyr) was reported to be associated with enhanced RV-C binding and increased replication in vitro. The aim of this study was to examine rs6967330 genotypes and mRNA expression of CDHR3 in relation to presence of rhinovirus and clinical symptoms in children with acute wheezing and compare to a group of age-matched healthy children.
Methods:
rs6967330;G>A was genotyped (n = 216), and CDHR3 mRNA expression was measured in peripheral blood leukocytes (n = 69) from a subgroup of children wheezing with RV infection acute and at a follow-up visit 2-3 months later, and in healthy controls. Standardized TaqMan assays were used.
Results:
The risk allele rs6967330-A was over-represented in the wheezing group (P < .001). Reduced mRNA levels of CDHR3 were found in children with acute wheezing as compared to the control group (P = .001). Children with the rs6967330 genotypes AA/AG showed the largest differences in CDHR3 expression between acute and follow-up visit (P < .04).
Conclusions:
Preschool children with RV-induced wheezing were shown to have reduced CDHR3 mRNA levels, which might result in an increased permeability of the epithelial layers of the airways and thereby an increased vulnerability. Thus, measuring CDHR3 mRNA levels might help to identify a more severe phenotype of wheezing preschool children.
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