Asthma and lower airway disease
Interleukin-1 receptor–like 1 polymorphisms are associated with serum IL1RL1-a, eosinophils, and asthma in childhood

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Background

IL-1 receptor–like 1 (IL1RL1) is a membrane receptor involved in TH2 inflammatory responses and eosinophilia. Single nucleotide polymorphisms (SNPs) in IL1RL1 have been associated with blood eosinophil counts in a genome-wide association study and with asthma in family-based and case-control studies.

Objective

We assessed in the prospective birth cohort Prevention and Incidence of Asthma and Mite Allergy (PIAMA) whether IL1RL1 SNPs associate with levels of its soluble transcript IL1RL1 (IL1RL1-a) in serum, blood eosinophil counts, and asthma prevalence from birth to age 8 years, and whether IL1RL1-a serum levels associate with blood eosinophil counts.

Methods

Fifteen IL1RL1 SNPs were genotyped. Serum IL1RL1-a levels were measured in 2 independent subsets within PIAMA, at 4 and 8 years. Blood eosinophil counts were measured in 4-year-old children.

Results

In 2 independent subsets of children, 13 of 15 SNPs were associated with serum IL1RL1-a levels at ages 4 and 8 years with a consistent direction of effect for each allele. Rs11685480 allele A and rs1420102 allele A were significantly associated with lower numbers of blood eosinophils. In the total cohort, rs1041973 allele A was associated with a decreased risk of developing asthma (odds ratio, 0.70; 95% CI, 0.54-0.90). Rs1420101, recently identified in a genome-wide association study in the Icelandic population, was not associated with asthma in this study. IL1RL1-a levels were not associated with eosinophil counts.

Conclusion

We demonstrate that IL1RL1 polymorphisms are associated with serum IL1RL1-a, blood 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.

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  • 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.

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