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Gene-gene interaction in regulatory T-cell function in atopy and asthma development in childhood

Bottema, Renske W.B., Kerkhof, Marjan, Reijmerink, Naomi E., Thijs, Carel, Smit, Henriette A., van Schayck, Constant P., Brunekreef, Bert, van Oosterhout, Antoon J., Postma, Dirkje S., Koppelman, Gerard H.·2010·Journal of Allergy and Clinical Immunology
DOI 10.1016/j.jaci.2010.04.024
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Abstract

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…

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Metadata

Authors
Bottema, R. W. B., Kerkhof, M., Reijmerink, N. E., Thijs, C., Smit, H. A., van Schayck, C. P., Brunekreef, B., van Oosterhout, A. J., Postma, D. S., & Koppelman, G. H.
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2010-08
Volume
126
Issue
2
Pages
338-346.e10
ISSN
0091-6749
DOI
10.1016/j.jaci.2010.04.024
Cited by
44
References
1
Language
en
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