Dept of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Eur Respir J. 2018 Mar 8;51(3). doi: 10.1183/13993003.01377-2017. Print 2018 Mar.
() is an important asthma gene. (Epi)genetic regulation of protein expression has not been established. We assessed the association between single nucleotide polymorphisms (SNPs), methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma.Associations of SNPs with asthma were determined in the Dutch Asthma Genome-wide Association Study cohort and three European birth cohorts, BAMSE (Children/Barn, Allergy, Milieu, Stockholm, an Epidemiological survey), INMA (Infancia y Medio Ambiente) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy), participating in the Mechanisms of the Development of Allergy study. We performed blood DNA methylation quantitative trait locus (QTL) analysis (n=496) and (epi)genome-wide protein QTL analysis on serum IL1RL1-a levels (n=1462). We investigated the association of CpG methylation with asthma (n=632) and IL1RL1-a levels (n=548), with subsequent causal inference testing. Finally, we determined the association of IL1RL1-a levels with asthma and its clinical characteristics (n=1101). asthma-risk SNPs strongly associated with methylation (rs1420101; p=3.7×10) and serum IL1RL1-a levels (p=2.8×10). methylation was not associated with asthma or IL1RL1-a levels. IL1RL1-a levels negatively correlated with blood eosinophil counts, whereas there was no association between IL1RL1-a levels and asthma.In conclusion, asthma-associated SNPs strongly regulate methylation and serum IL1RL1-a levels, yet neither these methylation CpG sites nor IL1RL1-a levels are associated with asthma.
（）是一个重要的哮喘基因。（表观遗传）尚未建立蛋白质表达的调控。我们评估了单核苷酸多态性（SNP）、甲基化和血清 IL1RL1-a 蛋白水平之间的关联，并旨在确定哮喘中的因果途径。在荷兰哮喘全基因组关联研究队列和三个欧洲出生队列（BAMSE[儿童/巴恩、过敏、环境、斯德哥尔摩，一项流行病学调查]、INMA[儿童与环境]和 PIAMA[预防和哮喘和螨虫过敏的发病率]）中确定了与哮喘相关的 SNP。我们进行了血液 DNA 甲基化定量性状（QTL）分析（n=496）和血清 IL1RL1-a 水平的（表观遗传）全基因组 QTL 分析（n=1462）。我们研究了 CpG 甲基化与哮喘（n=632）和 IL1RL1-a 水平（n=548）的关联，并进行了随后的因果推断检验。最后，我们确定了 IL1RL1-a 水平与哮喘及其临床特征（n=1101）的关联。哮喘风险 SNP 与甲基化（rs1420101；p=3.7×10）和血清 IL1RL1-a 水平（p=2.8×10）强烈相关。甲基化与哮喘或 IL1RL1-a 水平无关。IL1RL1-a 水平与血液嗜酸性粒细胞计数呈负相关，而 IL1RL1-a 水平与哮喘之间没有关联。总之，与哮喘相关的 SNP 强烈调节甲基化和血清 IL1RL1-a 水平，但这些甲基化 CpG 位点和 IL1RL1-a 水平均与哮喘无关。
