BACKGROUND: Regulatory T-cell dysfunction is associated with development of the complex genetic conditions atopy and asthma. Therefore, we hypothesized that single nucleotide polymorphisms in genes involved in the development and function of regulatory T cells are associated with atopy and asthma development. OBJECTIVE: To evaluate main effects and gene-gene interactions of haplotype tagging single nucleotide polymorphisms of genes involved in regulatory T-cell function-IL6, IL6R, IL10, heme-oxygenase 1 (HMOX1), IL2, Toll-like receptor 2 (TLR2), TGFB1, TGF-beta receptor (TGFBR)-1, TGFBR2, IL2RA, and forkhead box protein 3 (FOXP3)-in relation to atopy and asthma. METHODS: Single-locus and multilocus associations with total IgE (3rd vs 1st tertile); specific IgE to egg, milk, and indoor allergens; and asthma were evaluated by chi(2) tests and the multifactor dimensionality-reduction method in 3 birth cohorts (Allergenic study). RESULTS: Multiple statistically significant multilocus associations existed. IL2RA rs4749926 and TLR2 rs4696480 associated with IgE in both age groups tested (1-2 and 6-8 years). TGFBR2 polymorphisms associated with total and specific IgE in both age groups and with asthma. TGFBR2 rs9831477 associated with specific IgE for milk at age 1 to 2 years and indoor allergens at age 6 to 8 years. For milk-specific IgE, interaction between TGFBR2 and FOXP3 polymorphisms was confirmed by logistic regression and consistent in 2 birth cohorts and when stratified for sex, supplying internal replications. CONCLUSION: Genes involved in the development and function of regulatory T cells, specifically IL2RA, TLR2, TGFBR2, and FOXP3, associate with atopy and asthma by gene-gene interaction. Modeling of multiple gene-gene interactions is important to unravel further the genetic susceptibility to atopy and asthma. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
BACKGROUND: Regulatory T-cell dysfunction is associated with development of the complex genetic conditions atopy and asthma. Therefore, we hypothesized that single nucleotide polymorphisms in genes involved in the development and function of regulatory T cells are associated with atopy and asthma development. OBJECTIVE: To evaluate main effects and gene-gene interactions of haplotype tagging single nucleotide polymorphisms of genes involved in regulatory T-cell function-IL6, IL6R, IL10, heme-oxygenase 1 (HMOX1), IL2, Toll-like receptor 2 (TLR2), TGFB1, TGF-beta receptor (TGFBR)-1, TGFBR2, IL2RA, and forkhead box protein 3 (FOXP3)-in relation to atopy and asthma. METHODS: Single-locus and multilocus associations with total IgE (3rd vs 1st tertile); specific IgE to egg, milk, and indoor allergens; and asthma were evaluated by chi(2) tests and the multifactor dimensionality-reduction method in 3 birth cohorts (Allergenic study). RESULTS: Multiple statistically significant multilocus associations existed. IL2RArs4749926 and TLR2rs4696480 associated with IgE in both age groups tested (1-2 and 6-8 years). TGFBR2 polymorphisms associated with total and specific IgE in both age groups and with asthma. TGFBR2rs9831477 associated with specific IgE for milk at age 1 to 2 years and indoor allergens at age 6 to 8 years. For milk-specific IgE, interaction between TGFBR2 and FOXP3 polymorphisms was confirmed by logistic regression and consistent in 2 birth cohorts and when stratified for sex, supplying internal replications. CONCLUSION: Genes involved in the development and function of regulatory T cells, specifically IL2RA, TLR2, TGFBR2, and FOXP3, associate with atopy and asthma by gene-gene interaction. Modeling of multiple gene-gene interactions is important to unravel further the genetic susceptibility to atopy and asthma. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Authors: Cintia Rodrigues Marques; Gustavo No Costa; Thiago Magalhães da Silva; Pablo Oliveira; Alvaro A Cruz; Neuza Maria Alcantara-Neves; Rosemeire L Fiaccone; Bernardo L Horta; Fernando Pires Hartwig; Esteban G Burchard; Maria Pino-Yanes; Laura C Rodrigues; Maria Fernanda Lima-Costa; Alexandre C Pereira; Mateus H Gouveia; Hanaisa P Sant Anna; Eduardo Tarazona-Santos; Maurício Lima Barreto; Camila Alexandrina Figueiredo Journal: Eur J Hum Genet Date: 2017-01-25 Impact factor: 4.246
Authors: Kyung Won Kim; Kyung Eun Lee; Jung Yeon Hong; Mi Na Kim; Won Il Heo; Myung Hyun Sohn; Kyu-Earn Kim Journal: Lung Date: 2011-07-22 Impact factor: 2.584
Authors: Nathalie Acevedo; Annika Sääf; Cilla Söderhäll; Erik Melén; Jami Mandelin; Christina Orsmark Pietras; Sini Ezer; Piia Karisola; Johanna Vendelin; Gustav Boije af Gennäs; Jari Yli-Kauhaluoma; Harri Alenius; Erika von Mutius; Gert Doekes; Charlotte Braun-Fahrländer; Josef Riedler; Marianne van Hage; Mauro D'Amato; Annika Scheynius; Göran Pershagen; Juha Kere; Ville Pulkkinen Journal: PLoS One Date: 2013-04-02 Impact factor: 3.240