title: Definition of human interleukin-4 receptor alpha chain haplotypes and allelic association with atopy markers.
abstract: Cumulative evidence indicates that the human interleukin-4 receptor alpha chain gene (IL-4Ralpha, CD124) is highly polymorphic in contrast to other cytokine receptor genes. Our group recently identified the IL-4Ralpha variant R551 as being strongly associated with decreased kidney allograft survival. Due to the key immunoregulatory role of IL-4 and controversial reports on the association of IL-4Ralpha variants with atopy, we present here the development of polymerase chain reaction-primer sets for sequence-specific amplification of all seven hitherto described amino acid polymorphisms, and we investigated 158 blood donors prospectively. By using an Expectation-Maximization algorithm, we calculated the presence of 11 putative human IL-4Ralpha haplotypes and identified 4 putative IL-4Ralpha haplotypes with a cumulative frequency of >90%. None of the polymorphisms showed a significant association with the phenotype atopy. All mutant alleles showed a trend toward decreased total IgE levels. This association was only significant (p < 0.05; Mann-Whitney U-test) for the A375, R406, and P478 variants in non-atopic blood-donors (n = 90), presumably due to the high variance of IgE levels among the smaller group of atopic individuals. We postulate that IL-4Ralpha mutations are associated to different extents with a decrease in function of the receptor but do not present a major atopy locus.
authors.affiliation: Institute of Clinical Immunology and Transfusion Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Hackstein
authors.forename: H
authors.initials: H
authors.lastname: Hofmann
authors.forename: A
authors.initials: A
authors.lastname: Bohnert
authors.forename: G
authors.initials: G
authors.lastname: Bein
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005787:Gene Frequency; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology*; D015810:Linkage Disequilibrium; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D019948:Receptors, Interleukin-4 / Q000737:chemistry / Q000235:genetics*
chemical_list: D017931:DNA Primers; D005819:Genetic Markers; D019948:Receptors, Interleukin-4