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半乳糖凝集素-3凝集素结构域中的一个非同义多态性与对β-内酰胺类抗生素的过敏反应相关。

A non-synonymous polymorphism in galectin-3 lectin domain is associated with allergic reactions to beta-lactam antibiotics.

作者信息

Cornejo-García J A, Romano A, Guéant-Rodríguez R M, Oussalah A, Blanca-López N, Gaeta F, Tramoy D, Josse T, Doña I, Torres M J, Canto G, Blanca M, Guéant J-L

机构信息

INSERM U-954, University of Lorraine and University Hospital Center (CHU) of Nancy, Nancy, France.

Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain.

出版信息

Pharmacogenomics J. 2016 Feb;16(1):79-82. doi: 10.1038/tpj.2015.24. Epub 2015 Apr 14.

DOI:10.1038/tpj.2015.24
PMID:25869013
Abstract

Genetic predictors of beta-lactam (BL) allergy are mostly related to Immunoglobulin E (IgE) synthesis and atopy. Despite this context, little attention has been devoted to genes of IgE/FcɛRI pathway, such as galectin-3, a β-galactoside-binding lectin, which binds to IgE. We evaluated the association of LGALS3 polymorphisms with BL allergy in 395 Spanish and 198 Italian cases, compared with 310- and 339-matched controls, respectively. The rs11125 predicted BL allergy with an odds ratio of 4.0 in Spanish population (P<0.0001). This association was replicated with an odds ratio of 5.1 in Italian population (P<0.0001); rs11125 predicted also increased serum level of total IgE in Spanish controls. These data are consistent with the predicted deleterious influence of Gln>His substitution produced by rs11125 on galactose-binding activity of galectin-3. In conclusion, LGALS3 is the strongest genetic predictor of BL allergy reported so far. This association reflects the influence of genes of IgE/FcɛRI pathway in this pathology.

摘要

β-内酰胺(BL)过敏的遗传预测因素大多与免疫球蛋白E(IgE)合成和特应性有关。尽管如此,IgE/FcɛRI途径的基因,如与IgE结合的β-半乳糖苷结合凝集素半乳糖凝集素-3,却很少受到关注。我们评估了LGALS3基因多态性与395例西班牙人和198例意大利人BL过敏的关联,分别与310例和339例匹配的对照进行比较。rs11125在西班牙人群中预测BL过敏的比值比为4.0(P<0.0001)。这种关联在意大利人群中以5.1的比值比得到重复(P<0.0001);rs11在西班牙对照中也预测总IgE血清水平升高。这些数据与rs11125产生的Gln>His替代对半乳糖凝集素-3的半乳糖结合活性的预测有害影响一致。总之,LGALS3是迄今为止报道的BL过敏最强的遗传预测因素。这种关联反映了IgE/FcɛRI途径基因在这种病理中的影响。

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