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

JA Revez; L Bain; B Chapman; JE Powell; R Jansen; DL Duffy; JY Tung; AAGC Collaborators; MC Matheson; GB Marks; J Hui; P Le Souëf; P Danoy; S Baltic; DR Nyholt; M Jenkins; C Hayden; J Beilby; F Cheah; PA Madden; AC Heath; JL Hopper; B Musk; SR Leeder; EH Walters; A James; G Jones; MJ Abramson; CF Robertson; SC Dharmage; MA Brown; PJ Thompson; BW Penninx; PM Visscher; EJC De Geus; DI Boomsma; DA Hinds; NG Martin; GW Montgomery; MAR Ferreira

Journal article

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

JA Revez, L Bain, B Chapman, JE Powell, R Jansen, DL Duffy, JY Tung, AAGC Collaborators, MC Matheson, GB Marks, J Hui, P Le Souëf, P Danoy, S Baltic, DR Nyholt, M Jenkins, C Hayden, J Beilby, F Cheah, PA Madden Show all

Genes and Immunity | SPRINGERNATURE | Published : 2013

DOI: 10.1038/gene.2013.38

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 polym..

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University of Melbourne Researchers

Mark Jenkins Author

Haydn Walters Author

Shyamali Dharmage Author

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COMPREHENISVE MODEL FOR COLORECTAL CANCER RISK

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Grants

Awarded by National Institute of Mental Health

Funding Acknowledgements

We thank all the participants of the Asthma and Twin moles studies: Ann Eldridge, Marlene Grace, Kerrie McAloney (sample collection); Melinda Richter, Lisa Bowdler, Steven Crooks (DNA processing); David Smyth, Harry Beeby, Daniel Park (IT support). Funding was provided by the Australian National Health and Medical Research Council (NHMRC, 613627). The NTR/NESDA data described in this paper were funded by the US National Institute of Mental Health (RC2 MH089951, PI Sullivan) as part of the American Recovery and Reinvestment Act of 2009. MARF is supported by a Career Development Fellowship from the NHMRC.