Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma

Neda Farahi, Ellie Paige, Jozef Balla, Emily Prudence, Ricardo C. Ferreira, Mark Southwood, Sarah L. Appleby, Per Bakke, Amund Gulsvik, Augusto A. Litonjua, David Sparrow, Edwin K. Silverman, Michael H. Cho, John Danesh, Dirk S. Paul, Daniel F. Freitag*, Edwin R. Chilvers

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

The Asp358Ala variant in the interleukin-6 receptor (IL-6R) gene has been implicated in asthma, autoimmune and cardiovascular disorders, but its role in other respiratory conditions such as chronic obstructive pulmonary disease (COPD) has not been investigated. The aims of this study were to evaluate whether there is an association between Asp358Ala and COPD or asthma risk, and to explore the role of the Asp358Ala variant in sIL-6R shedding from neutrophils and its proinflammatory effects in the lung. We undertook logistic regression using data from the UK Biobank and the ECLIPSE COPD cohort. Results were meta-analyzed with summary data from a further three COPD cohorts (7,519 total cases and 35,653 total controls), showing no association between Asp358Ala and COPD (OR=1.02 [95% CI: 0.96, 1.07]). Data from the UK Biobank showed a positive association between the Asp358Ala variant and atopic asthma (OR=1.07 [1.01, 1.13]). In a series of in vitro studies using blood samples from 37 participants, we found that shedding of sIL-6R from neutrophils was greater in carriers.

Original languageEnglish
Article numberddx053
Pages (from-to)1584-1596
Number of pages13
JournalHuman Molecular Genetics
Volume26
Issue number8
DOIs
Publication statusPublished - 15 Apr 2017
Externally publishedYes

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