Background: Several studies have documented a substantial genetic component in the aetiology of allergic diseases, and a number of atopy susceptibility loci have been suggested. One of these loci is 3q21 where linkage to multiple atopy phenotypes has been reported. This region harbours the CD86 gene encoding the costimulatory B7.2 protein. The costimulatory system, consisting of receptor proteins, cytokines and associated factors, activates T cells and regulate the immune response upon allergen challenge. Methods: We sequenced the CD86 gene in atopic patients from 10 families that showed evidence of linkage to 3q21. Identified polymorphisms were analyzed in a subsequent family based association study of two independent Danish samples comprising 135 and 100 atopic case-parents trio families, respectively. Functional analysis of the costimulatory effect on cytokine production was performed in an autologous cell-based system based on cells expressing CD86 variants. Results: Two polymorphisms were identified encoding the amino-acid changes Ile179Val and Ala304Thr, respectively. Significant associations were observed between the Ile179Val polymorphism and allergy phenotypes in both samples (e.g.: asthma, p=0.004 in the two samples combined). The under-transmitted (protective) Val179 allele was found to induce higher production of both Th1 cytokines (IL-2, TNF-α, INF-γ) and Th2 cytokines (IL-4, IL-5) than the over-transmitted (risk) Ile179 allele, suggesting a functional impact of the polymorphism. Conclusion: The CD86 gene, and specifically the Ile179Val polymorphism, may be a novel aetiological factor in the development of asthma and related allergic disorders.
- family based association study
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.