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. 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.
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. 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.
Authors: Albert M Levin; Rasika A Mathias; Lili Huang; Lindsey A Roth; Denise Daley; Rachel A Myers; Blanca E Himes; Isabelle Romieu; Mao Yang; Celeste Eng; Julie E Park; Karla Zoratti; Christopher R Gignoux; Dara G Torgerson; Joshua M Galanter; Scott Huntsman; Elizabeth A Nguyen; Allan B Becker; Moira Chan-Yeung; Anita L Kozyrskyj; Pui-Yan Kwok; Frank D Gilliland; W James Gauderman; Eugene R Bleecker; Benjamin A Raby; Deborah A Meyers; Stephanie J London; Fernando D Martinez; Scott T Weiss; Esteban G Burchard; Dan L Nicolae; Carole Ober; Kathleen C Barnes; L Keoki Williams Journal: J Allergy Clin Immunol Date: 2012-11-10 Impact factor: 10.793
Authors: Justin Mostecki; Suzanne L Cassel; Walter T Klimecki; Debra A Stern; Judit Knisz; Sachiyo Iwashita; Penelope Graves; Rachel L Miller; Maartje van Peer; Marilyn Halonen; Fernando D Martinez; Donata Vercelli; Paul B Rothman Journal: J Immunol Date: 2011-07-27 Impact factor: 5.422
Authors: Leonardo A Pinto; Martin Depner; Norman Klopp; Thomas Illig; Christian Vogelberg; Erika von Mutius; Michael Kabesch Journal: Respir Res Date: 2010-02-24
Authors: Jayanta Gupta; Elisabet Johansson; Jonathan A Bernstein; Ranajit Chakraborty; Gurjit K Khurana Hershey; Marc E Rothenberg; Tesfaye B Mersha Journal: J Allergy Clin Immunol Date: 2016-06-11 Impact factor: 10.793