Mechanisms of Allergy
Association between polymorphisms in caspase recruitment domain containing protein 15 and allergy in two German populations,☆☆

https://doi.org/10.1067/mai.2003.1336Get rights and content

Abstract

Background: Early exposure to microbial matter such as LPS may influence the development of asthma and allergies by activation of innate immunity pathways as indicated by studies in farming environments. Recently, polymorphisms in caspase recruitment domain containing protein 15 (CARD15), an intracellular LPS receptor protein, have been associated with Crohn's disease. Because these polymorphisms lead to changes in LPS recognition, they may affect the development of asthma and allergies. Objective: We genotyped a large population of German schoolchildren (N = 1872) from East and West Germany for 3 functional relevant CARD15 polymorphisms for their role in the development of asthma and allergy. Methods: By use of parental questionnaires, skin prick testing, pulmonary function tests, bronchial challenge tests, and measurements of serum IgE levels, children were phenotyped for the presence of atopic diseases. Genotyping was performed with PCR-based restriction enzyme assays. To assess associations between atopic phenotypes and genotypes standard statistical procedures were applied. Results: Children with the polymorphic allele C2722 had a more than 3-fold risk to develop allergic rhinitis (P < .001) and an almost 2-fold risk for atopic dermatitis (P < .05). Furthermore, the T2104 allele was associated with an almost 2-fold risk for allergic rhinitis (P < .05). When a C insertion at position 3020 was present, the risk of atopy increased by 50% (P < .05) and serum IgE levels were elevated (P < .01). Conclusion: The shared genetic background between Crohn's disease and atopy may indicate that an impaired recognition of microbial exposures results in an insufficient downregulation of excessive immune responses, giving rise to either TH2 dominated allergies or TH1 related Crohn's disease. (J Allergy Clin Immunol 2003;111:813-7.)

Section snippets

Subjects

Between 1995 and 1996, a cross-sectional study was conducted in Munich, West Germany, and Dresden, East Germany, to assess the prevalence of asthma and allergies in schoolchildren aged 9 to 11 years.9 Parental questionnaires for self-completion were sent through the schools to the families. Children underwent skin prick testing, pulmonary function testing, and bronchial challenge with hyperosmolar saline (4.5%) at their schools. Blood was collected for serum IgE measurements and DNA extraction.

Results

All available blood samples in Munich (N = 1161) and a random sample of 50% of all available blood samples in Dresden (N = 711) were genotyped for the 3 SNPs in the CARD15 gene previously reported to be associated with Crohn's disease.5, 6, 7 No selection bias could be detected between children genotyped for this study and those who were not (Tables I and II). Furthermore, no significant difference was present between children genotyped for CARD15 polymorphisms in Munich and Dresden (Table I,

Discussion

In this study we showed that 3 polymorphisms in the CARD15 gene previously related to the development of Crohn's disease are also associated with atopic diseases. This observation was consistent in 2 population samples from East and West Germany. The strongest association was observed with allergic rhinitis, in which 2 CARD15 polymorphisms independently increased the risk to develop the disease by 2- to 3-fold. From these results we conclude that even though the frequency of CARD15

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Supported by German Ministry of Education and Research (BMBF)/National Genome Research Network (NGFN): Research grant BMBF 01GS 0122 (NGFN).

☆☆

Reprint requests: Michael Kabesch, MD, Children's University Hospital, Ludwig Maximilians University Munich, Lindwurmstrasse 4, D-80337 München, Germany.

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