Abstract
The MUC5B promoter polymorphism (rs35705950) has been associated with interstitial lung abnormalities (ILA) in white participants from the general population; whether these findings are replicated and influenced by the ILA subtype is not known. We evaluated the associations between the MUC5B genotype and ILA in cohorts with extensive imaging characterisation.
We performed ILA phenotyping and MUC5B promoter genotyping in 5308 and 9292 participants from the AGES-Reykjavik and COPDGene cohorts, respectively.
We found that ILA was present in 7% of participants from the AGES-Reykjavik, 8% of non-Hispanic white participants from COPDGene and 7% of African-American participants from COPDGene. Although the MUC5B genotype was strongly associated (after correction for multiple testing) with ILA (OR 2.1, 95% CI 1.8–2.4, p=1×10−26), there was evidence of significant heterogeneity between cohorts (I2=81%). When narrowed to specific radiologic subtypes, (e.g. subpleural ILA), the MUC5B genotype remained strongly associated (OR 2.6, 95% CI 2.2–3.1, p=1×10−30) with minimal heterogeneity (I2=0%). Although there was no evidence that the MUC5B genotype influenced survival, there was evidence that MUC5B genotype improved risk prediction for possible usual interstitial pneumonia (UIP) or a UIP pattern in non-Hispanic white populations.
The MUC5B promoter polymorphism is strongly associated with ILA and specific radiologic subtypes of ILA, with varying degrees of heterogeneity in the underlying populations.
Abstract
The MUC5B genotype is associated with specific subtypes of ILA, with varying heterogeneity in underlying populations http://ow.ly/pcmH30dRsZ7
Footnotes
This article has supplementary material available from erj.ersjournals.com.
Support statement: COPDGene is supported by NIH Award Number R01 HL089897 and R01 HL089856. R.K. Putman is supported by NIH Grant Number T32 HL007633. G. Gudmundsson is supported by the Oddur Olafsson Fund, project grant 141513-051 from the Icelandic Research Fund and Landspitali Scientific Fund A-2015-030 and A-2016-023. M. Nishino is supported by NIH Grant Number K23 CA157631. J.C. Ross is supported by NIH Grant Number K25 HL130637. R. San José Estépar is supported by NIH Grant Numbers: K25 HL104085 and R01 HL116473. E.R. Miller is supported by NIH Grant Number T32 HL007633. Y. Yamada is supported by project grant 141513-051 from the Icelandic Research Fund and Landspitali Scientific Fund A-2015-030. S. El-Chemaly is supported by NIH Grant Number R01 HL130275. B.A. Raby is supported by NIH Grant Numbers: U01 AI095219, R01 HL0866601, R01 HL118455, R01 HL123546, R01 HL130974 and P01 HL132825. M.H. Cho is supported by NIH Grant Number R01 HL113264. I.O. Rosas is supported by NIH Grant Numbers: R01 HL130974, R01 HL129920 and P01 HL114501. G.R. Washko is supported by NIH Grant Number: R01 HL122464 and R01 HL116473. D.A. Schwartz is supported by NIH Grant Numbers: R25 ES025476, P01 HL092870, R01 HL097163, R33 HL120770, UH2 HL123442 and the Veterans Administration Grant Number I01 BX001534. E.K. Silverman is supported by NIH Grants: R01 HL089856, R01 HL113264, R33 HL120794 and P01 HL114501. The Age, Gene/Environment Susceptibility-Reykjavik Study was supported by NIA grant: 27120120022C, NIH contracts N01-AG-1-2100 and HHSN27120120022C, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association) and the Althingi (the Icelandic Parliament). V. Gudnason is supported by NIA grant: 27120120022C and project grant 141513-051 from the Icelandic Research Fund. G.M. Hunninghake and this work were supported by NIH Grant Numbers: R01 HL111024, R01 HL130974 and project grant 141513-051 from the Icelandic Research Fund. Funding information for this article has been deposited with the Crossref Funder Registry.
Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com
- Received March 14, 2017.
- Accepted May 31, 2017.
- The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2017.
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