期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 127, 期 3, 页码 750-U394出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2010.12.014
关键词
IL1RL1; IL1RL1-a; eosinophils; asthma; atopy; children
资金
- Dutch Asthma Foundation [3.4.01.26, 3.2.06.022, 3.2.09.081JU]
- Zon-Mw Netherlands [912-03-031]
- NWO Spinoza premium of Prof Dr D. S. Postma
- Stichting Astma Bestrijding [2009/009]
- ministry of the environment
- Netherlands Asthma Fund
- GlaxoSmithKline
- AstraZeneca
- Netherlands Asthma Foundation
- European Union
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. (J Allergy Clin Immunol 2011;127:750-6.)
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