ICAM1 amino-acid variant K469E is associated with paediatric bronchial asthma and elevated sICAM1 levels

Abstract

Intercellular adhesion molecule-1 (ICAM1) acts as ligand for β2-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. © 2006 Nature Publishing Group. All rights reserved.