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A functional CD86 polymorphism associated with asthma and related allergic disorders
Thomas Juhl Corydon1, Annette Haagerup, Thomas Gryesten Jensen
1Institute of Human Genetics, the Bartholin Building, University of Aarhus, DK-8000 Aarhus C, Denmark.
Journal of Medical Genetics
|May 22, 2007
Summary
A specific gene variant, CD86 Ile179Val, is linked to increased risk of asthma and allergies. This genetic factor influences immune responses, suggesting a new target for understanding allergic disease development.
Area of Science:
- Immunogenetics
- Allergy Research
- Molecular Biology
Background:
- Allergic diseases have a significant genetic basis, with specific chromosomal regions like 3q21 implicated in atopy.
- The CD86 gene, located in the 3q21 region, encodes the B7.2 costimulatory protein crucial for T cell activation and immune regulation during allergen exposure.
Purpose of the Study:
- To investigate the role of the CD86 gene in the aetiology of allergic diseases.
- To identify and analyze genetic variations within CD86 associated with atopy susceptibility.
Main Methods:
- Sequencing of the CD86 gene in families with linkage to 3q21.
- Family-based association studies using two independent Danish cohorts (135 and 100 trios).
- Functional analysis of CD86 variants in an autologous cell system to assess cytokine production.
Main Results:
- Two CD86 polymorphisms identified: Ile179Val and Ala304Thr.
- The Ile179Val polymorphism showed significant association with allergy phenotypes, including asthma (p = 4 x 10(-3)).
- The Val179 allele conferred protection by inducing higher Th1 and Th2 cytokine production compared to the risk Ile179 allele.
Conclusions:
- The CD86 gene, particularly the Ile179Val polymorphism, represents a potential novel aetiological factor in asthma and allergic disorders.
- This finding highlights the importance of costimulatory molecules in the genetic predisposition to allergies.
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