Interleukin-4 and interleukin-13 pathway genetics affect disease susceptibility, serum immunoglobulin E levels, and gene expression in asthma
Interleukin-4 and interleukin-13 pathway genetics affect disease susceptibility, serum immunoglobulin E levels, and gene expression in asthma
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IL-4 和 IL-13 通路遗传学影响哮喘的疾病易感性、血清免疫球蛋白 E 水平和基因表达
DOI：
10.1016/j.anai.2014.05.004
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发表时间：
2014-08-01
影响因子：
5.9
通讯作者：
Li, Li
中科院分区：
文献类型：
--
作者：
Li, Jia;Lin, Li-hui;Li, Li
背景：哮喘是一种常见的免疫疾病，其特征是IgE水平升高。列鲁金（IL）-4和IL-13途径是IgE调节的核心，并且先前的研究报告了与哮喘相关的IL-4/IL-13信号的许多遗传变异，但很少有人集中在基因到基因的相互作用上，但很可能对疾病的复杂性有助于疾病的综合效果：SNPRING of SNPRENS SNPRING of SNPRENS of SNSPRING of 7 uncelist of 7 unceins of 7 uncerist）（儿童中的敏感性，总血清IgE水平和基因表达。 523）和总血清IgE水平和基因表达在患有哮喘的儿童中测量：哮喘儿童具有更多风险基因型的可能性。在没有测试的多态性的儿童中，平均IgE水平从携带7种风险基因型的儿童的儿童中的最低71.07 kU/L增加到901.7 kU/L。基因表达分析表明，患有4个SNP的患者（RS2243250，RS1800925，RS1805010和RS3224011）具有较高的IL-4，IL-13和STAT6的表达水平。此外，血清IgE水平通常与IL-4（r = 0.236，p = .011）和IL-13（r = 0.211，p = .021）表达式良好相关； IL-4表达与IL-13（r = 0.962，p = .000）和STAT6（r = 0.190，p = .022）的表达和STAT6表达与IL-4RA表达相关（r = 0.904，p = .000）.conconconclusion：这些数据表明，多种SNP的结合可能会影响疾病。只有对IL-4/IL-13途径中变体的组合分析才能显示哮喘中多个基因的功能相互作用。 （c）2014美国过敏，哮喘和免疫学学院。由Elsevier Inc.发布的所有权利保留。
Background: Asthma is a common immune disorder characterized by increased IgE levels. The interleukin (IL)-4 and IL-13 pathway is central for IgE regulation, and previous studies have reported many genetic variants of IL-4/IL-13 signaling in relation to asthma, but few have focused on the gene-to-gene interactions that are likely to contribute to disease complexity.Objective: To assess the combined effects of 7 functional single-nucleotide polymorphisms (SNPs) on asthma susceptibility, total serum IgE levels, and gene expression in children.Methods: Seven SNPs (rs2243250, rs1800925, rs1805010, rs324011, rs2251746, rs2494262, and rs2427837) were genotyped children with asthma (n = 500) and a control group (n = 523), and total serum IgE levels and gene expressions were measured in children with asthma.Results: Children with asthma had a likelier possibility of carrying more risk genotypes. Mean IgE levels increased from the minimum of 71.07 KU/L in children with no tested polymorphisms to a maximum of 901.7 KU/L in children carrying 7 risk genotypes. Gene expression analysis showed that patients with 4 SNPs (rs2243250, rs1800925, rs1805010, and rs3224011) had higher expression levels of IL-4, IL-13, and STAT6. Moreover, serum IgE level generally correlated well with IL-4 (r = 0.236, P = .011) and IL-13 (r = 0.211, P = .021) expressions; IL-4 expression correlated positively with IL-13 (r = 0.962, P = .000) and STAT6 (r = 0.190, P = .022) expressions, and STAT6 expression correlated with IL-4RA expression (r = 0.904, P = .000).Conclusion: These data suggest that combinations of multiple SNPs might magnify the impact on disease risk. Only a combined analysis of the variants in the IL-4/IL-13 pathway could show the functional interplay of multiple genes in asthma. (C) 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.