Genetic regulation of IL1RL1 methylation and IL1RL1-a protein levels in asthma

Dijk, F. Nicole and Xu, Chengjian and Melén, Erik and Carsin, Anne-Elie and Kumar, Asish and Nolte, Ilja M. and Gruzieva, Olena and Pershagen, Goran and Grotenboer, Neomi S. and Savenije, Olga E. M. and Antó, Josep Maria and Lavi, Iris and Dobaño, Carlota and Bousquet, Jean and van der Vlies, Pieter and van der Valk, Ralf J. P. and de Jongste, Johan C. and Nawijn, Martijn C. and Guerra, Stefano and Postma, Dirkje S. and Koppelman, Gerard H.. (2018) Genetic regulation of IL1RL1 methylation and IL1RL1-a protein levels in asthma. The European respiratory journal, 51 (3). p. 1701377.

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Official URL: https://edoc.unibas.ch/62228/

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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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Exposome Science (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Exposome Science (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Kumar, Ashish
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:02 Jul 2018 09:28
Deposited On:02 Jul 2018 09:28

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