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,43 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% Cl, 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. Conclusion: The data indicate that within the IL-4/IL,43 pathway, genetic variants in the STAT6 gene significantly contribute to the regulation of serum IgE levels.