A signal transducer and activator of transcription 6 haplotype influences the regulation of serum IgE levels
| Autor: | David Carr, Irene Schmid, Michaela Schedel, Erika von Mutius, Norman Klopp, Daniel Stachel, Thomas Illig, Bernd Woitsch, Stephan K. Weiland, Michael Kabesch, Christian Fritzsch |
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| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Immunology Population Molecular Sequence Data Single-nucleotide polymorphism Immunoglobulin E Atopy Polymorphism (computer science) Internal medicine medicine Immunology and Allergy Humans education Child STAT6 education.field_of_study Polymorphism Genetic biology Base Sequence Haplotype NF-kappa B medicine.disease Endocrinology Haplotypes biology.protein STAT protein Trans-Activators STAT6 Transcription Factor |
| Zdroj: | The Journal of allergy and clinical immunology. 114(5) |
| ISSN: | 0091-6749 |
| Popis: | Background Because of its central role in the IL-4/IL-13 pathway, the intracellular signaling molecule signal transducer and activator of transcription 6 (STAT6) may be crucial for IgE production in asthma and allergy. Objective We analyzed the association between polymorphisms in the STAT6 gene and the regulation of serum IgE levels. Methods In a population of 1120 German schoolchildren (age 9-11 years), we genotyped 6 previously identified polymorphisms spanning the STAT6 gene by using the matrix-assisted laser desorption ionization–time of flight mass spectrometry method. Haplotypes were estimated and population-derived IgE percentiles (50% IgE > 60 IU/mL, 66% IgE > 115 IU/mL, and 90% IgE > 457 IU/mL) were modeled as outcome variables in haplotype-trend regression analysis. Results Polymorphisms located in intron 2 (C2892T) and the 3′ untranslated region (T12888C) significantly and consistently contributed to elevated total serum IgE levels. One STAT6 haplotype showed increased odds ratios of 1.58 (95% CI, 1.08-2.32; P = .020), 1.82 (95% CI, 1.19-2.77; P = .006), and 3.92 (95% CI, 1.93-7.96; P = .0002) for elevated IgE levels at percentiles 50%, 66%, and 90%, respectively. Because C2892T is located within a nuclear factor κB transcription factor binding site, a functional role of this polymorphism is very likely. Conclusion The data indicate that within the IL-4/IL-13 pathway, genetic variants in the STAT6 gene significantly contribute to the regulation of serum IgE levels. |
| Databáze: | OpenAIRE |
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