Background. The CD14 gene has an important role in the detection of inflammatory provoking pathogens and in the ensuing signaling of the innate immune response. We assessed the role of CD14 C-159T, G-1359T in the expression of asthma, croup, and allergy in Canadian school children of ages 6 to 14 years. Methods. Children attending schools in a rural community participated in a cross-sectional survey of respiratory health. Following consent, we conducted clinical assessments to collect buccal swabs for genotyping and perform skin prick testing (SPT) to determine atopic status. Genotyping and SPT results were available for 533 and 499 children, respectively. Separate multivariable analyses that included both polymorphisms were conducted for each phenotype. Results. The prevalence of asthma, allergy, and croup was 18.6%, 22.4%, and 6.6%, respectively. Children with the T/T variant of CD14 G-1359T were more likely to have physician diagnosed asthma (26.8%). Children with C/C variant of CD14 C-159T had a significantly lower prevalence of croup (2.6%). Haplotype analyses of the two CD14 polymorphisms showed that individuals with the T|T haplotype combination were significantly more likely to have asthma ( ). Conclusions. In this study, CD14 variants are important for the expression of croup and asthma but not atopy. 1. Introduction Respiratory conditions such as asthma and croup are leading causes of hospitalization and emergency room use by children [1–3]. Asthma and allergy are common childhood conditions, and both genetic and environmental factors influence their expression [1]. The inflammatory airway responses associated with these conditions result from the stimulation by external agents of the TLR4 inflammatory pathway through genes such as CD14 located on the surface of immune response cells in the lungs as well as other organs. Both TLR4 and CD14 genes are codependent with MD2 in their roles as signalers of other mediators in the innate response to pathogens [1]. Unlike TLR4 A896G, a functional polymorphism in the Toll signaling pathway, whose primary response on the cell membrane is to the presence of lipopolysaccharide (LPS) from gram-negative bacteria, the CD14 gene appears to have a broader response to pathogen recognition [4–6]. It has a central role in innate immunity, as it can interact with several ligands, including LPS from gram-negative bacteria, components from gram-positive bacteria, fungi, and viruses [5]. CD14 has also been suspected to be a crucial link between innate and adaptive immunity in response to environmental antigens [3].
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