Research
Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA)
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* Corresponding author: NM Probst-Hensch Nicole.Probst@usz.ch
1 Molecular Epidemiology/Cancer Registry, Institutes of Social and Preventive Medicine & Surgical Pathology, University Hospital Zurich, Switzerland
2 Division of Medical Molecular Genetics and Gene Diagnostics, Institute of Medical Genetics, University of Zurich, Switzerland
3 Division of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, Germany
4 Division of Allergology, University Hospital, Basel, Switzerland
5 Departement of Pneumology, University Hospital, Basel, Switzerland
6 GSF-National Research Center for Environment and Health, Institute of Epidemiology, Munich, Germany
7 Institute of Social- und Preventive Medicine, University Basel, Switzerland
Clinical and Molecular Allergy 2006, 4:9 doi:10.1186/1476-7961-4-9
Published: 7 June 2006Abstract
Background
Atopy and allergic phenotypes are biologically characterized by an imbalanced T helper cell response skewed towards a type 2 (TH2) immune response associated with elevated serum immunoglobulin E (IgE) levels. Polymorphisms in cytokine genes might modulate regulation of the TH1/TH2 balance. We thus aimed at reproducing our previous findings from a European study population on the association of various cytokine polymorphisms with self-reported hay fever as well as increased total and specific IgE levels in two comparable study populations.
Methods
Two prospective Caucasian cohorts were used. In the Basel center of the European Community Respiratory Health Survey (ECRHS, n = 418) ten distinct cytokine polymorphisms of putative functional relevance were genotyped. In the Swiss cohort Study on Air Pollution And Lung Disease In Adults (SAPALDIA, n = 6003) two cytokine polymorphisms were genotyped. The associations of these polymorphisms with atopy were estimated by covariance and logistic regression analysis.
Results
We confirmed IL4, IL10, IL6 and IL18 as candidate genes for atopic health outcomes. In the large, well-characterized SAPALDIA cohort the IL6(-174G>C) and IL18(-137G>C) polymorphisms were associated with circulating total IgE concentrations in subjects with hay fever. The IL18(-137G>C) polymorphism was also associated with the prevalence of hay fever.
Conclusion
Comprehensive characterization of genetic variation in extended cytokine candidate gene regions is now needed. Large study networks must follow to investigate the association of risk patterns defined by genetic predisposing and environmental risk factors with specific atopic phenotypes.