期刊
PEDIATRIC PULMONOLOGY
卷 52, 期 11, 页码 1435-1442出版社
WILEY
DOI: 10.1002/ppul.23834
关键词
asthma & early wheeze; biomarkers; early onset wheeze; epidemiology; genetics; IL-4 polymorphism; nonatopic uncontrolled severe wheeze; phenotype; rs2070874; viral-induced wheeze
资金
- Fondation de France-Fondation Stallergnes
- Chancellerie des Universites-Legs Poix (UPMC)
- Societe Francaise d'Allergologie
- Novartis Pharma France
BackgroundChildhood recurrent wheezing and consequently asthma corresponds to various phenotypes. Our aim was to link genetic variants of asthma candidate genes to the phenotypes of early onset wheezing. Study designWe included very young consecutive children presenting with recurrent wheezing who had been evaluated for the severity of wheezing, associated atopic comorbidities, and tested for biomarkers of atopy and inflammation. All were genotyped for 16 single nucleotide polymorphisms (SNPs) linked with asthma or atopy. An unsupervised hierarchical bottom-up method was used for clustering the phenotypes and a multinomial logistic regression was performed for each individual SNP. ResultsWe replicated the three phenotypes previously described Trousseau Asthma Program in 317 children aged 21.57.9 months: cluster 1 (nonatopic uncontrolled severe wheeze), n=207, a severe viral-induced wheeze, cluster 2 (atopic multiple trigger wheeze), n=61, with multiple allergic comorbidities, and cluster 3 (episodic viral wheeze), n=49, a mild viral-induced wheeze. The TT-genotype of the IL-4 rs2070874 polymorphism was significantly associated with the nonatopic uncontrolled severe wheeze compared to the episodic viral wheeze (OR 7.9; CI95% [2.5-25.3]; P=0.001). ConclusionAssociation between the TT-genotype of IL-4 rs2070874 polymorphism and a severe phenotype of viral-induced wheeze further underlines the role IL-4 plays in the inflammation pathway leading to viral respiratory infections.
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