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白细胞介素-13 和 -18 启动子多态性对天然橡胶乳胶过敏医护人员的影响。

Impact of interleukin-13 and -18 promoter polymorphisms in health care workers with natural rubber latex allergy.

机构信息

Institute for Prevention and Occupational Medicine of the German Social Accident Insurance - Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany.

出版信息

J Toxicol Environ Health A. 2012;75(8-10):515-24. doi: 10.1080/15287394.2012.675302.

Abstract

It is a matter of debate whether single nucleotide polymorphisms (SNP) in the promoter region of interleukin (IL)-13, an IgE regulator, and IL-18, an inducer of immune responses, modulating the respective protein expression, are accompanied by an increased risk of atopy, allergic asthma, and total IgE levels. The suspected associations were noted in health care workers (HCW) with and without latex allergy. IL-13 (-1055C>T) and three IL-18 (-656T>G, -607C>A, -137G>C) SNP were studied in 523 HCW with natural rubber latex (NRL) exposure and diagnosis in the late 1990s. Three hundred and thirty-four HCW displayed NRL sensitization and allergic symptoms, 93 with latex-allergic asthma, and 189 HCW with neither symptoms nor NRL sensitization. SNP analyses were performed by real-time polymerase chain reaction (PCR) using newly developed LightCycler assays. Analysis of IL-13 -1055C>T by analysis of variance (ANOVA) revealed significantly elevated total IgE levels in HCW carrying the CT or TT variant compared with the CC variant. None of the studied SNP showed an association with NRL-specific IgE. The IL-18 variants -656GG and -607CC displayed 99.5% linkage disequilibrium. Frequencies of alleles -656GG and -607CC were elevated in HCW with NRL asthma (48.4%) compared with HCW without symptoms (37.6%). In contrast, IL-18 -137G>C variants displayed an overall homogenous distribution. The association between the IL-13 -1055T allele and elevated total IgE levels confirms the role of a genetic background for total IgE regulation. The studied IL-18 SNP demonstrated no significant association with the clinical outcome, total IgE, or specific IgE in HCW with natural rubber latex allergy.

摘要

目前仍存在争议,即白细胞介素(IL)-13 启动子区域的单核苷酸多态性(SNP)和 IL-18 免疫反应诱导物的 SNP 是否会改变相应蛋白的表达,并导致特应性、变应性哮喘和总 IgE 水平增加。在有和没有乳胶过敏的医护人员(HCW)中已经注意到了这些可疑的相关性。在 20 世纪 90 年代末,对 523 名接触天然橡胶乳胶(NRL)且有 NRL 过敏诊断的 HCW 进行了 IL-13(-1055C>T)和三个 IL-18(-656T>G、-607C>A、-137G>C)SNP 研究。334 名 HCW 显示 NRL 致敏和过敏症状,93 名 HCW 有乳胶变应性哮喘,189 名 HCW 既无症状也无 NRL 致敏。通过新开发的 LightCycler 测定法,采用实时聚合酶链反应(PCR)进行 SNP 分析。通过方差分析(ANOVA)对 IL-13-1055C>T 的分析表明,与 CC 变异体相比,携带 CT 或 TT 变异体的 HCW 的总 IgE 水平显著升高。研究的 SNP 均与 NRL 特异性 IgE 无关联。IL-18 变体 -656GG 和 -607CC 显示出 99.5%的连锁不平衡。与无症状的 HCW(37.6%)相比,NRL 哮喘的 HCW 中-656GG 和-607CC 等位基因的频率升高(48.4%)。相反,IL-18-137G>C 变体显示出总体均匀的分布。IL-13-1055T 等位基因与总 IgE 水平升高之间的关联证实了遗传背景对总 IgE 调节的作用。在天然橡胶乳胶过敏的 HCW 中,研究的 IL-18 SNP 与临床结局、总 IgE 或特异性 IgE 无显著关联。

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