Asthma and lower airway diseaseInterleukin-1 receptor–like 1 polymorphisms are associated with serum IL1RL1-a, eosinophils, and asthma in childhood
Section snippets
Study design
This study was performed in the Dutch multicenter birth cohort study PIAMA. Recruitment took place in 1996 and 1997. A screening questionnaire was distributed to 10,232 pregnant women attending 1 of 52 prenatal clinics in The Netherlands. On the basis of this screening, 7862 women (2779 with allergy and 5083 without allergy) were invited to participate in the study; 3963 live-born children participated the study (1237 with a mother with allergy were defined as high-risk, and 2726 children with
Descriptives
In total, parents of 4146 children gave informed consent. The prevalence of asthma at age 8 years was 3.6%. Serum IL1RL1-a levels were collected in 2 independent groups, 1 at age 4 years (n = 314; 302 children also had blood eosinophil counts) and 1 at age 8 years (n = 292; Fig 1). Genotypes of IL1RL1 were available in 2014 children after exclusion of children of non-Dutch descent. General characteristics of the study population are presented in Table I. Geometric mean IL1RL1-a level was 0.13
Discussion
This prospective birth cohort study shows that polymorphisms in IL1RL1 are associated with IL1RL1-a serum levels at 2 different time points (ages 4 and 8 years) in 2 independent subsets of children and with blood eosinophil counts at 4 years of age. Interestingly, we observe a consistent direction of effect of each associated allele with IL1RL1-a at ages 4 and 8 years and the number of eosinophils at age 4 years. IL1RL1 polymorphisms are also associated with asthma development in childhood.
References (29)
- et al.
A novel IL-1 family cytokine, IL-33, potently activates human eosinophils
J Allergy Clin Immunol
(2008) - et al.
Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors–insight into heterotrimeric IL-1 signaling complexes
Structure
(2009) - et al.
IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines
Immunity
(2005) - et al.
Soluble ST2 blocks interleukin-33 signaling in allergic airway inflammation
J Biol Chem
(2007) - et al.
The IL-33/ST2 pathway: therapeutic target and novel biomarker
Nat Rev Drug Discov
(2008) - et al.
Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction
Nat Genet
(2009) - et al.
Expression and function of the ST2 gene in a murine model of allergic airway inflammation
Clin Exp Allergy
(2002) - et al.
Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses
J Exp Med
(1999) - et al.
Resolution of allergic inflammation and airway hyperreactivity is dependent upon disruption of the T1/ST2-IL-33 pathway
Am J Respir Crit Care Med
(2009) - et al.
Functional SNPs in the distal promoter of the ST2 gene are associated with atopic dermatitis
Hum Mol Genet
(2005)
Association of IL1RL1, IL18R1, and IL18RAP gene cluster polymorphisms with asthma and atopy
J Allergy Clin Immunol
Investigations into the role of ST2 in acute asthma in children
Tissue Antigens
Evidence of association of interleukin-1 receptor-like 1 gene polymorphisms with chronic rhinosinusitis
Am J Rhinol Allergy
Evaluation of candidate genes in a genome-wide association study of childhood asthma in Mexicans
J Allergy Clin Immunol
Cited by (0)
The Prevention and Incidence of Asthma and Mite Allergy study was supported by the Dutch Asthma Foundation (grant nos. 3.4.01.26, 3.2.06.022, and 3.2.09.081JU), the Zon-Mw Netherlands (grant no. 912-03-031), the NWO Spinoza premium of Prof Dr D. S. Postma, the “Stichting Astma Bestrijding” (grant no. 2009/009), and the ministry of the environment.
Disclosure of potential conflict of interest: J. C. de Jongste receives research support from the Netherlands Asthma Fund and ZonMW. D. S. Postma receives research support from GlaxoSmithKline and AstraZeneca and has consultant arrangements with AstraZeneca, Nycomed, and Chiesi. G. H. Koppelman receives research support from the Netherlands Asthma Foundation, GlaxoSmithKline, and the European Union. The rest of the authors have declared that they have no conflict of interest.