Screening of the Fc epsilon RI-beta-gene in a Swiss population of asthmatic children: no association with E237G and identification of new sequence variations.
ABSTRACT The gene of the beta subunit of the high affinity receptor for IgE (Fc epsilon RI-beta) encoded on chromosome 11q13 has recently been identified as a candidate gene for asthma and atopy. Two coding variations, E237G and I181L have been described as being associated with asthma and atopy. Our aim was to investigate a Swiss population of atopic and asthmatic children for variations in this gene.
We screened all 7 exons of the Fc epsilon RI-beta-gene in 224 atopic/asthmatic, 68 relatives and 159 control subjects using exon amplification by PCR and single strand conformation polymorphism (SSCP) analysis followed by fluorescence based DNA sequencing.
The sequence variant E237G was found in 3.7% in atopics and in 2.6% in the control population. None of the samples carried the I181L mutation. In addition, we characterised nine novel mutations (1 nonsense mutation, 2 missense mutations, mutation, 2 silent mutations, 4 intronic mutations).
Our results suggest that the E237G does not have a primary effect on the development of atopy and asthma, and thus excludes the Fc epsilon RI-beta locus from being a candidate gene directly involved in these diseases.
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ABSTRACT: Allergien sind weitverbreitete Erkrankungen, die einen sozialen und ökologischen Faktor darstellen. In den letzten Jahren zeigte sich ein Anstieg der Prävalenz allergischer Erkrankungen. Um dem entgegenwirken zu können, ist es wichtig, die Ursachen zu erforschen. Dabei spielen Assoziationsanalysen als Mittel der Identifikation von allergie-suszeptiblen Genen eine wichtige Rolle. Methoden: Es wurden insgesamt 16 Genvarianten in den Genen für IL4, IFNG, TLR4, CNS1, IL13, IRF1, IL4R untersucht und auf Assoziation mit dem IgE-Spiegel und der Atopieanamnese getestet. Ergebnisse: Es zeigten sich keine Assoziationen der untersuchten Varianten.
Article: Factors responsible for differences between asymptomatic subjects and patients presenting an IgE sensitization to allergens. A GA2LEN project.[show abstract] [hide abstract]
ABSTRACT: The synthesis of allergen-specific IgE is required for the development of allergic diseases including allergic rhinitis and allergic asthma (patients), but many individuals with allergen-specific IgE do not develop symptoms (asymptomatic subjects). Differences may exist between asymptomatic subjects and patients. Whether the presence of allergen-specific IgE translates into clinical allergy most likely depends on a complex interplay of multiple factors. These include a family history of atopy, the levels of total serum IgE and, allergen-specific IgE or IgG, epitope-specificity of IgE and their degree of polyclonality (mono- vs polysensitized), as yet unidentified serum factors, the balance of T regulatory cells (Treg) and Th1/Th2 cells, the polymorphisms of the high affinity receptor for IgE (FcepsilonRI) and other factors regulating the activation of FcepsilonRI-bearing cells. Asymptomatic subjects may be more often monosensitized than patients who may be more often polysensitized. There are many unanswered important questions that need to be addressed in order to better understand how IgE sensitization translates into clinical allergy. The assessment of differences between the asymptomatic and symptomatic groups of subjects represent one of the scientific programs of Global Allergy and Asthma European Network funded by the European Union and the hypotheses underlying these differences are presented in this paper.Allergy 07/2006; 61(6):671-80. · 6.27 Impact Factor