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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Genetic regulation of IL1RL1 methylation and IL1RL1 - A protein levels in asthma
European Respiratory Journal, Volume 51, No. 3, Article 1701377, Year 2018
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Description
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)genomewide 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. © ERS 2018.
Authors & Co-Authors
Xu, Cheng Jian
Netherlands, Groningen
Rijksuniversiteit Groningen
Melén, Erik
Sweden, Stockholm
Karolinska Institutet
Sweden, Stockholm
Region Stockholm
Sweden, Stockholm
Södersjukhuset
Nolte, Ilja Maria
Netherlands, Groningen
Rijksuniversiteit Groningen
Antò, Josep María
Spain, Barcelona
Instituto de Salud Global de Barcelona
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Spain, Barcelona
Institut Municipal D'investigacio Medica
Lavi, Iris
Spain, Barcelona
Instituto de Salud Global de Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Spain, Barcelona
Institut Municipal D'investigacio Medica
Dobaño, Carlota
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Bousquet, Jean J.
France, Montpellier
Centre Hospitalier Universitaire de Montpellier
van der Valk, Ralf J.P.
Netherlands, Rotterdam
Erasmus Mc
de Jongste, Johan C.
Netherlands, Rotterdam
Erasmus Mc
Nawijn, Martijn C.
Netherlands, Groningen
Rijksuniversiteit Groningen
Guerra, Stefano
Spain, Barcelona
Instituto de Salud Global de Barcelona
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Spain, Madrid
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
United States, Tucson
The University of Arizona
Koppelman, Gerard H.
Netherlands, Groningen
Universitair Medisch Centrum Groningen
Netherlands, Groningen
Rijksuniversiteit Groningen
Statistics
Citations: 23
Authors: 12
Affiliations: 14
Identifiers
Doi:
10.1183/13993003.01377-2017
ISSN:
09031936
Research Areas
Genetics And Genomics
Maternal And Child Health
Study Design
Cross Sectional Study
Cohort Study
Study Approach
Quantitative