Katarina Stenberg Hammar1,2,3, Katarzyna Niespodziana4, Marianne van Hage5, Juha Kere6,7, Rudolf Valenta4, Gunilla Hedlin1,2,3, Cilla Söderhäll1,3,6. 1. Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. 2. Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. 3. Centre of Allergy Research, Karolinska Institutet, Stockholm, Sweden. 4. Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. 5. Immunology and Allergy Unit, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 6. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden. 7. Molecular Neurology Research Program, University of Helsinki and Folkhälsan Institute of Genetics, Helsinki, Finland.
Abstract
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.
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 childrenwheezing 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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