ORIGINAL ARTICLE

Association of a STAT 6 haplotype with elevated serum IgE levels in a population based cohort of white adults

S Weidinger^1,6, N Klopp², S Wagenpfeil³, L Rümmler¹, M Schedel⁴, M Kabesch⁴, T Schäfer⁵, U Darsow¹, T Jakob^1,6, H Behrendt⁶, H E Wichmann², J Ring^1,6, T Illig²

¹ Department of Dermatology and Allergy Biederstein, Technical University Munich, Germany
² Institute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg, Germany
³ Institute for Medical Statistics and Epidemiology, Technical University Munich, Germany
⁴ University Childrens’ Hospital, Ludwig Maximilians University Munich, Germany
⁵ Institute of Social Medicine, Medical University Lübeck, Germany
⁶ Division of Environmental Dermatology and Allergy GSF/TUM, GSF National Research Center for Environment and Health & ZAUM Center for Allergy and Environment, Technical University Munich, Germany

Correspondence to:
Correspondence to:
Dr S Weidinger
Department of Dermatology and Allergy, Technical University Munich, Biedersteiner St. 29, 80802 Munich, Germany; weidinger{at}lrz.tum.de

Background: Several studies have shown linkage of chromosome 12q 13–24 with atopy related phenotypes. Among candidate genes in this region is STAT6 (signal transducer and activator of transcription), which is essential for Th2 cell differentiation, recruitment, and effector function.

Methods: We evaluated six polymorphisms of STAT6 for evidence of associations with serum IgE levels and atopic diseases in a population based cross sectional cohort of 1407 German adults. Genotyping was performed using the matrix assisted laser desorption ionisation–time of flight mass spectrometry method. Haplotypes were estimated using the SAS/Genetics module, and population-derived IgE percentiles (50% IgE>53 kU/l, 66% IgE>99 kU/l and 90% IgE>307 kU/l) were modelled as outcome variables in haplotype trend regression analysis.

Results: All polymorphisms were genotyped successfully. Haplotype reconstruction revealed 8/64 possible haplotypes, reaching estimated frequencies of 1% or more. One polymorphism in intron 2 (rs324011) showed a significant association with total serum IgE (p = 0.015). A STAT6 risk haplotype for elevated IgE showing odds ratios of 1.7 (p = 0.015) for IgE cut-off 100 kU/l, and 1.54 (p = 0.032), 1.6 (p = 0.025), and 2.54 (p = 0.007) for IgE percentiles 50%, 66%, and 90%, respectively was detected. The increased risk of this haplotype was confirmed by linear haplotype trend regression on log transformed IgE values (p = 0.007). Analysis further revealed a risk haplotype for specific sensitisation and a risk haplotype for asthma.

Conclusion: The data indicate that genetic variants within STAT6 contribute significantly to IgE regulation and manifestation of atopic diseases.

Abbreviations: IL, interleukin; RAST, radioallergosorbent test; SAP, shrimp alkaline phosphatase; SNP, single nucleotide polymorphism; STAT6, signal transducer and activator of transcription 6; TFB, transcription factor binding

Keywords: STAT6; atopy; IgE; polymorphisms; haplotype

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Sunyer, J., Forastiere, F., Pekkanen, J., Plana, E., Kolz, M., Pistelli, R., Jacquemin, B., Bruske-Hohlfeld, I., Pitsavos, Ch., Bellander, T., Koenig, W., Peters, A., on behalf of the AIRGENE Study Group, (2009). Interaction between smoking and the interleukin-6 gene affects systemic levels of inflammatory biomarkers. Nicotine Tob Res 11: 1347-1353 [Abstract] [Full Text]  
• Laumen, H., Saningong, A. D., Heid, I. M., Hess, J., Herder, C., Claussnitzer, M., Baumert, J., Lamina, C., Rathmann, W., Sedlmeier, E.-M., Klopp, N., Thorand, B., Wichmann, H.-E., Illig, T., Hauner, H. (2009). Functional Characterization of Promoter Variants of the Adiponectin Gene Complemented by Epidemiological Data. Diabetes 58: 984-991 [Abstract] [Full Text]  
• Jacquemin, B., Antoniades, C., Nyberg, F., Plana, E., Muller, M., Greven, S., Salomaa, V., Sunyer, J., Bellander, T., Chalamandaris, A.-G., Pistelli, R., Koenig, W., Peters, A. (2008). Common Genetic Polymorphisms and Haplotypes of Fibrinogen Alpha, Beta, and Gamma Chains Affect Fibrinogen Levels and the Response to Proinflammatory Stimulation in Myocardial Infarction Survivors: The AIRGENE Study. J Am Coll Cardiol 52: 941-952 [Abstract] [Full Text]  
• Sunyer, J., Pistelli, R., Plana, E., Andreani, M., Baldari, F., Kolz, M., Koenig, W., Pekkanen, J., Peters, A., Forastiere, F. (2008). Systemic inflammation, genetic susceptibility and lung function. Eur Respir J 32: 92-97 [Abstract] [Full Text]  
• Kolz, M., Koenig, W., Muller, M., Andreani, M., Greven, S., Illig, T., Khuseyinova, N., Panagiotakos, D., Pershagen, G., Salomaa, V., Sunyer, J., Peters, A., for the AIRGENE Study Group, (2008). DNA variants, plasma levels and variability of C-reactive protein in myocardial infarction survivors: results from the AIRGENE study. Eur Heart J 29: 1250-1258 [Abstract] [Full Text]  
• Bhanoori, M., Deenadayal, M., Kennedy, S., Shivaji, S. (2007). The G2964A 3'-untranslated region polymorphism of the signal transducer and activator of transcription 6 gene is associated with endometriosis in South Indian women. Hum Reprod 22: 1026-1030 [Abstract] [Full Text]  
• Schaeffer, L., Gohlke, H., Muller, M., Heid, I. M., Palmer, L. J., Kompauer, I., Demmelmair, H., Illig, T., Koletzko, B., Heinrich, J. (2006). Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet 15: 1745-1756 [Abstract] [Full Text]  
• Heid, I. M., Wagner, S. A., Gohlke, H., Iglseder, B., Mueller, J. C., Cip, P., Ladurner, G., Reiter, R., Stadlmayr, A., Mackevics, V., Illig, T., Kronenberg, F., Paulweber, B. (2006). Genetic Architecture of the APM1 Gene and Its Influence on Adiponectin Plasma Levels and Parameters of the Metabolic Syndrome in 1,727 Healthy Caucasians. Diabetes 55: 375-384 [Abstract] [Full Text]  
• Rabstein, S., Unfried, K., Ranft, U., Illig, T., Kolz, M., Rihs, H.-P., Mambetova, C., Vlad, M., Bruning, T., Pesch, B. (2006). Variation of the N-Acetyltransferase 2 Gene in a Romanian and a Kyrgyz Population. Cancer Epidemiol. Biomarkers Prev. 15: 138-141 [Abstract] [Full Text]