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白细胞介素-18基因多态性与青少年特发性关节炎及支气管哮喘的关联研究

Association study of polymorphisms within interleukin-18 in juvenile idiopathic arthritis and bronchial asthma.

作者信息

Heinzmann A, Gerhold K, Ganter K, Kurz T, Schuchmann L, Keitzer R, Berner R, Deichmann K A

机构信息

University Children's Hospital, University of Freiburg, Mathildenstrasse 1, 79106 Freiburg, Germany.

出版信息

Allergy. 2004 Aug;59(8):845-9. doi: 10.1111/j.1398-9995.2004.00538.x.

Abstract

BACKGROUND

Interleukin-18 (IL-18) plays an important role in the regulation of TH1 as well as TH2 immunologic responses and thus in the development of chronic inflammatory diseases. Positive association studies of polymorphisms in IL-18 with different diseases have underlined the involvement of IL-18 in the pathogenetics processes. Our interest was to test polymorphisms of IL-18 for association with a typical TH1-mediated disease--juvenile idiopathic arthritis--and the TH2-mediated disease bronchial asthma in Caucasian children.

METHODS

We genotyped five polymorphisms that were in association with chronic inflammatory diseases (-607C, -137C, 113G, 127T, and -133G). This was performed by restriction fragment length polymorphism in populations of asthmatic children, control individuals, and children with antinuclear antibodies (ANA)-positive juvenile idiopathic arthritis. Statistical analysis was performed by the Armitage trend test; haplotypes were calculated by the Arlequine program.

RESULTS

No significant association was found between any single nucleotide polymorphism or any haplotype and bronchial asthma or ANA-positive juvenile idiopathic arthritis.

CONCLUSION

We conclude that the effect of IL-18 in the immunologic context of diseases like bronchial asthma or juvenile arthritis might be too complex to be reflected in a simple one-way association study. Furthermore, the polymorphisms under investigation might be nonfunctional.

摘要

背景

白细胞介素-18(IL-18)在调节TH1以及TH2免疫反应中发挥重要作用,因而在慢性炎症性疾病的发展过程中也起着重要作用。对IL-18基因多态性与不同疾病的阳性关联研究强调了IL-18参与发病机制过程。我们感兴趣的是检测IL-18的基因多态性与白种人儿童中一种典型的TH1介导疾病——幼年特发性关节炎——以及TH2介导疾病支气管哮喘之间的关联。

方法

我们对与慢性炎症性疾病相关的5种多态性(-607C、-137C、113G、127T和-133G)进行基因分型。这是通过对哮喘儿童群体、对照个体以及抗核抗体(ANA)阳性幼年特发性关节炎儿童群体进行限制性片段长度多态性分析来完成的。采用阿米蒂奇趋势检验进行统计分析;单倍型通过Arlequine程序计算。

结果

未发现任何单核苷酸多态性或任何单倍型与支气管哮喘或ANA阳性幼年特发性关节炎之间存在显著关联。

结论

我们得出结论,IL-18在支气管哮喘或幼年关节炎等疾病的免疫背景中的作用可能过于复杂,无法在简单的单向关联研究中得以体现。此外,所研究的多态性可能不具备功能。

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