Departments of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J Allergy Clin Immunol. 2011 Mar;127(3):750-6.e1-5. doi: 10.1016/j.jaci.2010.12.014. Epub 2011 Feb 1.
IL-1 receptor-like 1 (IL1RL1) is a membrane receptor involved in T(H)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.
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.
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.
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.
We demonstrate that IL1RL1 polymorphisms are associated with serum IL1RL1-a, blood eosinophils, and asthma in childhood.
白细胞介素 1 受体样 1（IL-1RL1）是一种参与 T(H)2 炎症反应和嗜酸性粒细胞增多的膜受体。全基因组关联研究发现，IL-1RL1 中的单核苷酸多态性（SNP）与血液嗜酸性粒细胞计数有关，家族性和病例对照研究发现与哮喘有关。
我们在前瞻性出生队列预防和哮喘及螨变应性研究（PIAMA）中评估，IL-1RL1 SNP 是否与血清可溶性转录物 IL-1RL1（IL-1RL1-a）水平、血液嗜酸性粒细胞计数以及从出生到 8 岁的哮喘患病率相关，以及 IL-1RL1-a 血清水平是否与血液嗜酸性粒细胞计数相关。
共检测了 15 个 IL-1RL1 SNP。在 PIAMA 中，2 个独立的亚组分别在 4 岁和 8 岁时测量了血清 IL-1RL1-a 水平。在 4 岁的儿童中测量了血液嗜酸性粒细胞计数。
在 2 个独立的儿童亚组中，15 个 SNP 中有 13 个与 4 岁和 8 岁时的血清 IL-1RL1-a 水平相关，每个等位基因的效应方向一致。rs11685480 等位基因 A 和 rs1420102 等位基因 A 与较低的血液嗜酸性粒细胞计数显著相关。在整个队列中，rs1041973 等位基因 A 与哮喘发病风险降低相关（比值比，0.70；95%CI，0.54-0.90）。最近在冰岛人群全基因组关联研究中发现的 rs1420101 在本研究中与哮喘无关。IL-1RL1-a 水平与嗜酸性粒细胞计数无关。
我们证明 IL-1RL1 多态性与儿童时期的血清 IL-1RL1-a、血液嗜酸性粒细胞计数和哮喘有关。
