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.