Interleukin-1 receptor-like 1 polymorphisms are associated with serum IL1RL1-a, eosinophils, and asthma in childhood

Olga E. M. Savenije, Marjan Kerkhof, Naomi E. Reijmerink, Bert Brunekreef, Johan C. de Jongste, Henriette A. Smit, Alet H. Wijga, Dirkje S. Postma, Gerard H. Koppelman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

50 Citations (Scopus)

Abstract

Background: IL-1 receptor-like 1 (IL1RL1) is a membrane receptor involved in TH(2) 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.)

Original languageEnglish
Pages (from-to)750-U394
Number of pages12
JournalJournal of Allergy and Clinical Immunology
Volume127
Issue number3
DOIs
Publication statusPublished - Mar-2011

Keywords

  • IL1RL1
  • IL1RL1-a
  • eosinophils
  • asthma
  • atopy
  • children
  • ALLERGIC AIRWAY INFLAMMATION
  • GENE POLYMORPHISMS
  • IL-1 FAMILY
  • ST2 GENE
  • PATHWAY
  • CYTOKINE
  • PIAMA
  • ATOPY

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