Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich and Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Hum Immunol. 2010 Nov;71(11):1154-60. doi: 10.1016/j.humimm.2010.08.008. Epub 2010 Aug 22.
Asthma is a chronic pulmonary disorder that is characterized by airway inflammation and bronchial hyperreactivity. Several genetic loci have been associated with asthma, and some of these associations have been replicated in independent studies. However, larger population-based replication studies for the association of short tandem repeat (STR) polymorphisms with asthma are limited. In this study, we investigated the association of STR polymorphisms in genes encoding mast cell chymase (CMA1), uteroglobin (UGB), tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) with asthma and atopic phenotypes in the large population-based Swiss Cohort Study SAPALDIA. Our results show that the STR polymorphism in the CMA1 gene is associated with asthma and that this association is even stronger with atopic asthma. Similarly, we observed a weak association of the IL-4 2-allele with asthma that tended to be stronger for atopic asthma than for nonatopic asthma. This minor IL-4 2-allele was also associated with higher IgE levels, with a higher risk for a positive skin prick test and with a trend for a higher risk for bronchial hyperresponsiveness. These results support previous findings suggesting a role for CMA1 and IL-4 in atopic asthma and for IL-4 in atopy in general.
哮喘是一种慢性肺部疾病，其特征是气道炎症和支气管高反应性。几个遗传位点与哮喘有关，其中一些关联已在独立研究中得到复制。然而，与哮喘相关的短串联重复（STR）多态性的基于更大人群的复制研究是有限的。在这项研究中，我们研究了编码肥大细胞糜蛋白酶（CMA1）、尿促球蛋白（UGB）、肿瘤坏死因子-α（TNF-α）和白细胞介素-4（IL-4）的基因中的 STR 多态性与基于大人群的瑞士队列研究 SAPALDIA 中的哮喘和特应性表型的相关性。我们的结果表明，CMA1 基因中的 STR 多态性与哮喘有关，而这种关联在特应性哮喘中更为强烈。同样，我们观察到 IL-4 2-等位基因与哮喘的弱关联，对于特应性哮喘比非特应性哮喘更强。这种较小的 IL-4 2-等位基因也与更高的 IgE 水平相关，对皮肤点刺试验呈阳性的风险更高，并且支气管高反应性的风险也有增加的趋势。这些结果支持了先前的研究结果，表明 CMA1 和 IL-4 在特应性哮喘中以及 IL-4 在特应性中起作用。
