Flore Amat1,2,3,4, Malek Louha5, Marta Benet4,6,7, Tamazoust Guiddir1, Mélisande Bourgoin-Heck1,2, Philippe Saint-Pierre8, Colombe Paluel-Marmont1,2, Cécile Fontaine1, Nathalie Lambert1, Rémy Couderc5, Juan-Ramon Gonzalez4,6,7, Jocelyne Just1,2,3. 1. Department of Allergology-Centre de l'Asthme et des Allergies, Hôpital d'Enfants Armand Trousseau, Assistance Publique-Hôpitaux de Paris, Paris, France. 2. UPMC Univ Paris 06, Sorbonne Universités, Paris, France. 3. Equipe EPAR, Institut Pierre Louis d'Epidémiologie et de Santé Publique, UMR_S1136, INSERM, Faculté de Médecine Saint-Antoine, rue de Chaligny, Paris, France. 4. ISGlobal, Barcelona Institute for Global Health-Campus MAR, Barcelona Biomedical Research Park (PRBB) Doctor Aiguader, 88, 08003, Barcelona, Spain. 5. Laboratory of Biochemistry and Molecular Biology-Laboratoire de Biochimie et Biologie Moléculaire, Hôpital d'Enfants Armand Trousseau, Assistance Publique-Hôpitaux de Paris, Paris, France. 6. Universitat Pompeu Fabra (UPF), Barcelona, Spain. 7. CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. 8. Institut de Mathématiques de Toulouse, Université Toulouse III Paul Sabatier, Toulouse, France.
Abstract
BACKGROUND: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.
BACKGROUND: 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. STUDY DESIGN: 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. RESULTS: 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-4rs2070874 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). CONCLUSION: Association between the TT-genotype of IL-4rs2070874 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.