Puthothu B, Krueger M, Bernhardt M, Heinzmann A
University Children's Hospital, University of Freiburg, Germany.
Genes Immun. 2006 Jun;7(4):322-6. doi: 10.1038/sj.gene.6364302. Epub 2006 Apr 20.
Intercellular adhesion molecule-1 (ICAM1) acts as ligand for beta2-integrin molecules and mediates leucocyte trafficking to the site of inflammation. Intercellular adhesion molecule-1-deficient mice show impaired lymphocyte recruitment to the lung, less airway hyper-responsiveness and less lung inflammation than healthy controls. Thus, the aim of the study was to test common ICAM1 polymorphisms for association with paediatric asthma. Furthermore, we were interested in whether soluble ICAM1 (sICAM1) serum levels were in correlation with genotypes. The following polymorphisms in ICAM1 were genotyped on 352 children with asthma and 270 controls: rs5491 (resulting in the amino-acid exchange K56M), rs5493 (G241S), rs5498 (K469E), rs5030400 (R478W) and rs885743 in the 3'-untranslated region. In addition, sICAM1 serum levels were measured. Only K469E and rs885743 were present in our populations. K469E showed association with asthma (P = 0.0037 with Armitage's trend test). Haplotype analysis by FAMHAP using both polymorphisms revealed association with asthma by P < 0.000001. In addition, serum sICAM1 levels were correlated with K469E genotypes (P = 0.009 by Kruskal-Wallis test). We conclude from our data that K469KE is associated with paediatric asthma in the German population. Furthermore, the same polymorphism is correlated with serum levels of sICAM1. Functional analyses have to further clarify the pathophysiological mechanism conferred by the polymorphisms.
细胞间黏附分子-1（ICAM1）作为β2整合素分子的配体，介导白细胞向炎症部位的转运。与健康对照相比，细胞间黏附分子-1缺陷小鼠的淋巴细胞向肺部募集受损，气道高反应性降低，肺部炎症减轻。因此，本研究的目的是测试常见的ICAM1基因多态性与儿童哮喘的相关性。此外，我们还关注可溶性ICAM1（sICAM1）血清水平是否与基因型相关。对352例哮喘儿童和270例对照进行了ICAM1以下多态性的基因分型：rs5491（导致氨基酸替换K56M）、rs5493（G241S）、rs5498（K469E）、rs5030400（R478W）以及3'非翻译区的rs885743。此外，还测量了sICAM1血清水平。我们的人群中仅存在K469E和rs885743。K469E与哮喘相关（阿米蒂奇趋势检验P = 0.0037）。使用这两种多态性通过FAMHAP进行单倍型分析显示与哮喘相关，P < 0.000001。此外，血清sICAM1水平与K469E基因型相关（Kruskal-Wallis检验P = 0.009）。我们从数据中得出结论，K469KE与德国人群中的儿童哮喘相关。此外，相同的多态性与sICAM1的血清水平相关。功能分析必须进一步阐明这些多态性赋予的病理生理机制。
