Association of CCR5-delta32 Mutation with Reduced Risk of Nonatopic Asthma in Slovenian Children

Abstract

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.

Keywords:

• CCR5-delta32
• asthma
• atopy
• genotype
• phenotype
• genetics
• association study