Analysis of the Ser786Pro interleukin-4 receptor α allelic variant in allergic and nonallergic asthma and its functional consequences
Analysis of the Ser786Pro interleukin-4 receptor α allelic variant in allergic and nonallergic asthma and its functional consequences
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DOI：
10.1006/clim.2001.5082
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发表时间：
2001-09-01
影响因子：
8.6
通讯作者：
Hershey, GKK
中科院分区：
文献类型：
--
作者：
Andrews, RP;Burrell, L;Hershey, GKK
哮喘和其他特应性疾病影响了很大比例的人群。虽然哮喘的表型有很多因素，但也有很强的遗传易感性。IL-4是过敏性炎症的中枢介质。与IL-13一样，它是诱导IgE合成的主要细胞因子。此外，IL-4作用于Th0细胞并促进其分化为Th2细胞，从而产生更多的IL-4和IL-13，从而传播过敏级联反应。IL-4和IL-13都利用IL-4Rα作为其同源受体复合体的一个组成部分。已经描述了IL-4Rα基因的八个多态导致编码序列的氨基酸变化，其中几个与哮喘有关。本研究的中心目的是阐明Ser786Pro基因多态性在哮喘发病中的作用及其对IL-4R功能的影响。对196名哮喘患者和53名对照进行了Pro786基因分型。Pro786在普通人群中很少发生，等位基因频率为1.8%，因此不太可能在特应性或哮喘中起主要作用。Pro786等位基因频率在哮喘组为1.5%，对照组为2.8%。哮喘组分为过敏性哮喘和非过敏性哮喘，Pro786等位基因频率分别为1.7%和1.0%。这些数据提示Ser786Pro和Gin576Arg等位基因之间存在连锁不平衡，这与特应性疾病有关。为了研究该基因多态性对受体信号转导功能的影响，我们将人IL-4ra野生型和Pro786变异体分别导入小鼠B淋巴瘤细胞系。分离到的Ser786Pro多态不影响IL-4R功能。(C)2001年学术出版社。
Asthma and other atopic disorders affect a large percentage of the population. While many factors contribute to the phenotype of asthma, there is a strong genetic predisposition. IL-4 is a central mediator of allergic inflammation. Along with IL-13, it is the major cytokine responsible for the induction of IgE synthesis. Furthermore, IL-4 acts on Th0 cells and promotes their differentiation into Th2 cells resulting in the production of more IL-4 and IL-13, thereby propagating the allergic cascade. Both IL-4 and IL-13 utilize IL-4R alpha as a component of their cognate receptor complexes. Eight polymorphisms of the IL-4R alpha gene resulting in amino acid changes in the coding sequence have been described, and several have been associated with asthma. The central objective of this study was to elucidate the role of the Ser786Pro polymorphism in asthma and its impact on IL-4R function. One-hundred ninety-six individuals with asthma and 53 controls were genotyped for Pro786. Pro786 occurred infrequently in the general population with an allele frequency of 1.8% and, thus, is unlikely to play a major role in atopy or asthma. The Pro786 allele frequency was 1.5% in the asthma group and 2.8% in the control group. The asthma group was subdivided into allergic and nonallergic asthma, and the Pro786 allele frequencies were 1.7 and 1.0%, respectively. The data suggested linkage disequilibrium between Ser786Pro and the Gin576Arg allele, which is associated with atopy. In order to study the impact of the polymorphism on receptor signaling function, we transfected a mouse B lymphoma cell line with the wild-type and Pro786 variants of human IL-4Ra. The Ser786Pro polymorphism in isolation did not affect IL-4R function. (C) 2001 Academic Press.