Amat Flore, Louha Malek, Benet Marta, Guiddir Tamazoust, Bourgoin-Heck Mélisande, Saint-Pierre Philippe, Paluel-Marmont Colombe, Fontaine Cécile, Lambert Nathalie, Couderc Rémy, Gonzalez Juan-Ramon, Just Jocelyne
Department of Allergology-Centre de l'Asthme et des Allergies, Hôpital d'Enfants Armand Trousseau, Assistance Publique-Hôpitaux de Paris, Paris, France.
UPMC Univ Paris 06, Sorbonne Universités, Paris, France.
Pediatr Pulmonol. 2017 Nov;52(11):1435-1442. doi: 10.1002/ppul.23834. Epub 2017 Sep 26.
Childhood 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.
We 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.
We replicated the three phenotypes previously described Trousseau Asthma Program in 317 children aged 21.5 ± 7.9 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).
Association 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.
儿童复发性喘息以及由此引发的哮喘对应着多种表型。我们的目的是将哮喘候选基因的遗传变异与早发性喘息的表型联系起来。
我们纳入了连续就诊的非常年幼的复发性喘息儿童，对他们的喘息严重程度、相关的特应性合并症进行了评估，并检测了特应性和炎症的生物标志物。所有儿童均对与哮喘或特应性相关的16个单核苷酸多态性（SNP）进行了基因分型。采用无监督分层自下而上的方法对表型进行聚类，并对每个个体SNP进行多项逻辑回归分析。
我们在317名年龄为21.5±7.9个月的儿童中复制了先前特鲁索哮喘项目描述的三种表型：第1组（非特应性未控制的严重喘息），n = 207，为严重病毒诱导的喘息；第2组（特应性多触发因素喘息），n = 61，伴有多种过敏性合并症；第3组（发作性病毒喘息），n = 49，为轻度病毒诱导的喘息。与发作性病毒喘息相比，IL-4 rs2070874多态性的TT基因型与非特应性未控制的严重喘息显著相关（OR 7.9；95%CI[2.5 - 25.3]；P = 0.001）。
IL-4 rs2070874多态性的TT基因型与病毒诱导的严重喘息表型之间的关联进一步强调了IL-4在导致病毒性呼吸道感染的炎症途径中所起的作用。
