A signal transducer and activator of transcription 6 haplotype influences the regulation of serum IgE levels.
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 kappaB transcription factor binding site, a functional role of this polymorphism is very likely.


CONCLUSIONS
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.
Schedel
Michaela
M
University Children's Hospital, Ludwig Maximilian University-Munich, Lindwurmstrasse 4, D-80337 Munich, Germany.
Carr
David
D
Klopp
Norman
N
Woitsch
Bernd
B
Illig
Thomas
T
Stachel
Daniel
D
Schmid
Irene
I
Fritzsch
Christian
C
Weiland
Stephan K
SK
von Mutius
Erika
E
Kabesch
Michael
M
D001483:Base Sequence; D002648:Child; D006239:Haplotypes; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011110:Polymorphism, Genetic; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000235:genetics*
D016328:NF-kappa B; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D007073:Immunoglobulin E