Abstract
BackgroundAtopy 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.MethodsTwo 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.ResultsWe 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.ConclusionComprehensive 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.
Highlights
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
We have previously investigated a combination of cytokine polymorphisms that we judged to have a high likelihood of functional relevance, with regard to risk of atopy and hay fever in a subsample of the European Prospective Investigation into Cancer and Nutrition (EPIC) [4]
The European Community Respiratory Health Study (ECRHS) participants had a narrower age range and asthmatics had been over-sampled leading to increased proportions of hay fever, eczema cases, and atopy when compared to the SAPALDIA study cohort representative of the adult Swiss general population
Summary
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. We 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. In recent years polymorphisms in various cytokine genes have been identified and indication of functional relevance exists for some of them. They have been associated with atopic disorders such as hay fever, asthma, eczema or elevated IgE levels, though inconsistently in many cases. We have previously investigated a combination of cytokine polymorphisms that we judged to have a high likelihood of functional relevance, with regard to risk of atopy and hay fever in a subsample of the European Prospective Investigation into Cancer and Nutrition (EPIC) [4]. A novel finding of our study was the association of a protective heterozygous effect of the IL6(-174C>G) polymorphism with the risk for hay fever and with IgE levels in hay fever cases
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