A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk

Revez, J. A., Bain, L., Chapman, B., Powell, J. E., Jansen, R., Duffy, D. L., Tung, J. Y., AAGC Collaborators, Penninx, B. W., Visscher, P. M., De Geus, E. J. C., Boomsma, D. I., Hinds, D. A., Martin, N. G., Montgomery, G. W., Ferreira, M. A. R., Danoy, Patrick and Brown, Matthew A. (2013) A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk. Genes and Immunity, 14 7: 441-446. doi:10.1038/gene.2013.38

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Author Revez, J. A.
Bain, L.
Chapman, B.
Powell, J. E.
Jansen, R.
Duffy, D. L.
Tung, J. Y.
AAGC Collaborators
Penninx, B. W.
Visscher, P. M.
De Geus, E. J. C.
Boomsma, D. I.
Hinds, D. A.
Martin, N. G.
Montgomery, G. W.
Ferreira, M. A. R.
Danoy, Patrick
Brown, Matthew A.
Total Author Count Override 16
Title A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk
Journal name Genes and Immunity   Check publisher's open access policy
ISSN 1466-4879
1476-5470
Publication date 2013-10
Sub-type Article (original research)
DOI 10.1038/gene.2013.38
Open Access Status File (Author Post-print)
Volume 14
Issue 7
Start page 441
End page 446
Total pages 6
Place of publication London, United Kingdom
Publisher Nature Publishing
Collection year 2014
Language eng
Abstract The main genetic determinant of soluble interleukin 6 receptor (sIL-6R) levels is the missense variant rs2228145 that maps to the cleavage site of IL-6R. For each Ala allele, sIL-6R serum levels increase by ∼20 ng ml -1 and asthma risk by 1.09-fold. However, this variant does not explain the total heritability for sIL-6R levels. Additional independent variants in IL6R may therefore contribute to variation in sIL-6R levels and influence asthma risk. We imputed 471 variants in IL6R and tested these for association with sIL-6R serum levels in 360 individuals. An intronic variant (rs12083537) was associated with sIL-6R levels independently of rs4129267 (P=0.0005), a proxy single-nucleotide polymorphism for rs2228145. A significant and consistent association for rs12083537 was observed in a replication panel of 354 individuals (P=0.033). Each rs12083537:A allele increased sIL-6R serum levels by 2.4 ng ml -1. Analysis of mRNA levels in two cohorts did not identify significant associations between rs12083537 and IL6R transcription levels. On the other hand, results from 16 705 asthmatics and 30 809 controls showed that the rs12083537:A allele increased asthma risk by 1.04-fold (P=0.0419). Genetic risk scores based on IL6R regulatory variants may prove useful in explaining variation in clinical response to tocilizumab, an anti-IL-6R monoclonal antibody.
Keyword Allergy
eQTL
Expression
Disease
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
UQ Diamantina Institute Publications
 
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