title: Effects of common atopy-associated amino acid substitutions in the IL-4 receptor alpha chain on IL-4 induced phenotypes.
abstract: The human IL-4 receptor alpha chain gene (IL4R) is highly polymorphic and controversial reports have been published with respect to the association of different single nucleotide polymorphisms (SNPs) with atopy markers. Here we analyzed the functional and associational relevance of common IL4R coding SNPs. Transfection of B cell lines expressing the IL-4R variant V75+R576 did not result in enhanced IL-4 induced CD23 expression compared to cell lines expressing the wild type IL-4R alpha chain. Transfection of the IL-4R variant P503 into a murine T cell line did not influence IL-4 induced T-cell proliferation compared to wild type constructs. Analysis of six IL4R coding SNPs (I75V, E400A, C431R, S436L, S503P, Q576R) and common haplotypes (frequency >/=0.05%) in blood donors (n=300) did not indicate a significant association with elevated serum IgE level. Moreover, the most informative IL4R coding SNPs (I75V, C431R, Q576R) and related two- and three-point haplotypes (frequency >/=0.05%) were analyzed in a second, extended group of blood donors (n=689). Again, no significant association with elevated serum IgE was detectable. We conclude that common coding SNPs in the IL4R gene are unlikely to contribute significantly to increased IgE levels and variations outside the coding region may influence atopy susceptibility.
authors.affiliation: Institute of Clinical Immunology and Transfusion Medicine, Justus Liebig University, Langhansstrasse 7, 35392 Giessen, Germany, Izolda.Franjkovic@immunologie.med.uni-giessen.de
authors.forename: Izolda
authors.initials: I
authors.lastname: Franjkovic
authors.forename: Andre
authors.initials: A
authors.lastname: Gessner
authors.forename: Inke
authors.initials: I
authors.lastname: König
authors.forename: Karin
authors.initials: K
authors.lastname: Kissel
authors.forename: Anette
authors.initials: A
authors.lastname: Bohnert
authors.forename: Anne
authors.initials: A
authors.lastname: Hartung
authors.forename: Astrid
authors.initials: A
authors.lastname: Ohly
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Holger
authors.initials: H
authors.lastname: Hackstein
authors.forename: Gregor
authors.initials: G
authors.lastname: Bein
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006239:Haplotypes; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010641:Phenotype; D051381:Rats; D019948:Receptors, Interleukin-4 / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014162:Transfection
chemical_list: D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007073:Immunoglobulin E