PT  - JOURNAL ARTICLE
AU  - F. Nicole Dijk
AU  - Chengjian Xu
AU  - Erik Melén
AU  - Anne-Elie Carsin
AU  - Asish Kumar
AU  - Ilja M. Nolte
AU  - Olena Gruzieva
AU  - Goran Pershagen
AU  - Neomi S. Grotenboer
AU  - Olga E.M. Savenije
AU  - Josep Maria Antó
AU  - Iris Lavi
AU  - Carlota Dobaño
AU  - Jean Bousquet
AU  - Pieter van der Vlies
AU  - Ralf J.P. van der Valk
AU  - Johan C. de Jongste
AU  - Martijn C. Nawijn
AU  - Stefano Guerra
AU  - Dirkje S. Postma
AU  - Gerard H. Koppelman
TI  - Genetic regulation of <em>IL1RL1</em> methylation and IL1RL1-a protein levels in asthma
AID  - 10.1183/13993003.01377-2017
DP  - 2018 Mar 01
TA  - European Respiratory Journal
PG  - 1701377
VI  - 51
IP  - 3
4099  - http://erj.ersjournals.com/content/51/3/1701377.short
4100  - http://erj.ersjournals.com/content/51/3/1701377.full
SO  - Eur Respir J2018 Mar 01; 51
AB  - Interleukin-1 receptor–like 1 (IL1RL1) is an important asthma gene. (Epi)genetic regulation of IL1RL1 protein expression has not been established. We assessed the association between IL1RL1 single nucleotide polymorphisms (SNPs), IL1RL1 methylation and serum IL1RL1-a protein levels, and aimed to identify causal pathways in asthma.Associations of IL1RL1 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 IL1RL1 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 IL1RL1 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).IL1RL1 asthma-risk SNPs strongly associated with IL1RL1 methylation (rs1420101; p=3.7×10−16) and serum IL1RL1-a levels (p=2.8×10−56). IL1RL1 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 IL1RL1 SNPs strongly regulate IL1RL1 methylation and serum IL1RL1-a levels, yet neither these IL1RL1-methylation CpG sites nor IL1RL1-a levels are associated with asthma.Interleukin-1 receptor-like 1 (IL1RL1) SNPs regulate IL1RL1-methylation and serum IL1RL1-a levels, yet these effects are not related to asthma http://ow.ly/AStC30hSvGy