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A functional CD86 polymorphism associated with asthma and related allergic disorders.

ABSTRACT: 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, at which 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 regulates the immune response upon allergen challenge. METHODS: We sequenced the CD86 gene in patients with atopy from 10 families that showed evidence of linkage to 3q21. Identified polymorphisms were analysed in a subsequent family-based association study of two independent Danish samples, respectively comprising 135 and 100 trios of children with atopy and their parents. 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 (eg, asthma, p = 4 x 10(-3) in the two samples combined). The undertransmitted (protective) Val179 allele was found to induce higher production of both Th1 and Th2 cytokines than the overtransmitted (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.

SUBMITTER: Corydon TJ

PROVIDER: S-EPMC2597931 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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A functional CD86 polymorphism associated with asthma and related allergic disorders.

Corydon Thomas Juhl TJ Haagerup Annette A Jensen Thomas Gryesten TG Binderup Helle Glud HG Petersen Mikkel Steen MS Kaltoft Keld K Vestbo Jørgen J Kruse Torben Arvid TA Børglum Anders Dupont AD

Journal of medical genetics 20070518 8

<h4>Background</h4>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, at which 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 regulates the immune response upo ...[more]

PMID: 17513529

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Project description:OBJECTIVES:Pediatric asthma is heterogeneous with phenotypes that reflect differing underlying inflammation and pathophysiology. Little is known about the national prevalence of certain obesity- and allergy-related asthma phenotypes or associated characteristics. We therefore assessed the national prevalence, risk factors, and caregiver-reported severity of four asthma phenotypes: not-allergic-not-obese, allergic-not-obese, obese-not-allergic, and allergic-and-obese. METHODS:We analyzed data from the 2007-2008 National Survey of Children's Health (NSCH) of 10-17 year-olds with caregiver-reported asthma. We described sociodemographic and health risk factors of each phenotype and then applied logistic and ordinal regression models to identify associated risk factors and level of severity of the phenotypes. RESULTS:Among 4427 children with asthma in this NSCH cohort, the association between race and phenotype was statistically significant (p < 0.0001); white children with asthma were most likely to have allergic-not-obese asthma while black and Hispanic children with asthma were most likely to have the obese-nonallergic phenotype (p < 0.001). Attention-deficit disorder/attention-deficit hyperactivity disorder was more likely to be present in allergic-not-obese children (odds ratio (OR) 1.50, confidence interval (CI) 1.14-1.98, p = 0.004). The phenotype with the highest risk for more severe compared to mild asthma was the obese-and-allergic asthma phenotype (OR 3.34, CI 2.23-5.01, p < 0.001). CONCLUSIONS:Allergic-not-obese asthma comprised half of our studied asthma phenotypes, while obesity-related asthma (with or without allergic components) comprised one-fifth of asthma phenotypes in this cohort representative of the US population. Children with both obese and allergic asthma are most likely to have severe asthma. Future management of childhood asthma might consider more tailoring of treatment and management plans based upon different childhood asthma phenotypes.

Dataset Information

A functional CD86 polymorphism associated with asthma and related allergic disorders.

Publications

A functional CD86 polymorphism associated with asthma and related allergic disorders.

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