A signal transducer and activator of transcription 6 haplotype influences the regulation of serum IgE levels - 24/08/11
Reprint requests: Michael Kabesch, MD, University Children's Hospital, Ludwig Maximilian University Munich, Lindwurmstrasse 4, D-80337 München, Germany.Munich, Neuherberg, Erlangen, Leipzig, and Ulm, Germany
Résumé |
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.
Le texte complet de cet article est disponible en PDF.Key words : STAT6, atopy, IgE, IL-4 pathway, SNP
Abbreviations used : NF-κB, SNP, STAT6, TFB, UTR
Plan
| Supported by the German Ministry of Education and Research/National Genome Research Network research grants NGFN 01GS 0122 and NGFN IE-S08T03. |
Vol 114 - N° 5
P. 1100-1105 - novembre 2004 Retour au numéro
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