Berce Vojko, Repnik Katja, Potocnik Uros
Department of Pediatrics, General Hospital Murska Sobota, Murska Sobota, Slovenia.
J Asthma. 2008 Nov;45(9):780-4. doi: 10.1080/02770900802386024.
Asthma is one of the most common chronic diseases of childhood. Asthma results from the interaction of several genes and environmental influences. Viral infections are common triggers of asthma attacks, especially in nonatopic asthmatics. CCR5 is a chemokine receptor involved in the immune response against a number of viruses. A 32 base pair deletion (delta32) in the CCR5 receptor gene causes loss of gene function and is associated with several chronic diseases due to the resulting altered immunity. The results of the association studies exploring the role of the CCR5 receptor gene in asthma pathogenesis are contradictory. We studied 111 children aged between 5 and 18 years with mild or moderate persistent asthma; 75 of them were atopic and 36 had nonatopic asthma. We carried out allergy and spirometry tests, a bronchoprovocation test with methacholine and performed measurement of exhaled nitric oxide and genotyping for CCR5-delta32 mutation. Compared with 365 nonatopic, nonasthmatic controls we found significantly lower CCR5-delta32 allelic frequency in nonatopic asthmatics (p = 0.016, OR 0.139, 95% CI 0.02 to 0.984) but not in atopic asthmatics. CCR5-delta32 mutation protects against nonatopic asthma. This association offers new insights into the pathogenesis of an important asthma phenotype and could serve as useful information for the future research of new asthma management strategies.
哮喘是儿童期最常见的慢性疾病之一。哮喘是由多种基因与环境因素相互作用导致的。病毒感染是哮喘发作的常见诱因,尤其是在非特应性哮喘患者中。CCR5是一种参与针对多种病毒免疫反应的趋化因子受体。CCR5受体基因中的32个碱基对缺失(delta32)会导致基因功能丧失,并由于由此产生的免疫改变而与多种慢性疾病相关。探索CCR5受体基因在哮喘发病机制中作用的关联研究结果相互矛盾。我们研究了111名年龄在5至18岁之间的轻度或中度持续性哮喘儿童;其中75名是特应性哮喘患者,36名是非特应性哮喘患者。我们进行了过敏和肺功能测试、乙酰甲胆碱支气管激发试验,并测量了呼出一氧化氮以及对CCR5-delta32突变进行基因分型。与365名非特应性、非哮喘对照者相比,我们发现非特应性哮喘患者中CCR5-delta32等位基因频率显著更低(p = 0.016,比值比0.139,95%可信区间0.02至0.984),但在特应性哮喘患者中并非如此。CCR5-delta32突变可预防非特应性哮喘。这种关联为一种重要哮喘表型的发病机制提供了新见解,并可为未来新哮喘管理策略的研究提供有用信息。