ERJ Open Research (Feb 2024)
Association study of human leukocyte antigen variants and idiopathic pulmonary fibrosis
- Beatriz Guillen-Guio,
- Megan L. Paynton,
- Richard J. Allen,
- Daniel P.W. Chin,
- Lauren J. Donoghue,
- Amy Stockwell,
- Olivia C. Leavy,
- Tamara Hernandez-Beeftink,
- Carl Reynolds,
- Paul Cullinan,
- Fernando Martinez,
- Helen L. Booth,
- William A. Fahy,
- Ian P. Hall,
- Simon P. Hart,
- Mike R. Hill,
- Nik Hirani,
- Richard B. Hubbard,
- Robin J. McAnulty,
- Ann B. Millar,
- Vidya Navaratnam,
- Eunice Oballa,
- Helen Parfrey,
- Gauri Saini,
- Ian Sayers,
- Martin D. Tobin,
- Moira K.B. Whyte,
- Ayodeji Adegunsoye,
- Naftali Kaminski,
- Shwu-Fan Ma,
- Mary E. Strek,
- Yingze Zhang,
- Tasha E. Fingerlin,
- Maria Molina-Molina,
- Margaret Neighbors,
- X. Rebecca Sheng,
- Justin M. Oldham,
- Toby M. Maher,
- Philip L. Molyneaux,
- Carlos Flores,
- Imre Noth,
- David A. Schwartz,
- Brian L. Yaspan,
- R. Gisli Jenkins,
- Louise V. Wain,
- Edward J. Hollox
Affiliations
- Beatriz Guillen-Guio
- Department of Population Health Sciences, University of Leicester, Leicester, UK
- Megan L. Paynton
- Department of Population Health Sciences, University of Leicester, Leicester, UK
- Richard J. Allen
- Department of Population Health Sciences, University of Leicester, Leicester, UK
- Daniel P.W. Chin
- Department of Population Health Sciences, University of Leicester, Leicester, UK
- Lauren J. Donoghue
- Genentech, San Francisco, CA, USA
- Amy Stockwell
- Genentech, San Francisco, CA, USA
- Olivia C. Leavy
- Department of Population Health Sciences, University of Leicester, Leicester, UK
- Tamara Hernandez-Beeftink
- Department of Population Health Sciences, University of Leicester, Leicester, UK
- Carl Reynolds
- National Heart & Lung Institute, Imperial College London, London, UK
- Paul Cullinan
- National Heart & Lung Institute, Imperial College London, London, UK
- Fernando Martinez
- Department of Medicine, Weill Cornell Medicine, New York, NY, USA
- Helen L. Booth
- University College Hospital, University College London, London, UK
- William A. Fahy
- GlaxoSmithKline, London, UK
- Ian P. Hall
- School of Medicine, University of Nottingham, Nottingham, UK
- Simon P. Hart
- Hull York Medical School, University of Hull, Hull, UK
- Mike R. Hill
- MRC Population Health Unit, University of Oxford, Oxford, UK
- Nik Hirani
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
- Richard B. Hubbard
- School of Medicine, University of Nottingham, Nottingham, UK
- Robin J. McAnulty
- Division of Medicine, University College London, London, UK
- Ann B. Millar
- Bristol Medical School, University of Bristol, Bristol, UK
- Vidya Navaratnam
- Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK
- Eunice Oballa
- GlaxoSmithKline, London, UK
- Helen Parfrey
- Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK
- Gauri Saini
- School of Medicine, University of Nottingham, Nottingham, UK
- Ian Sayers
- Centre for Respiratory Research, NIHR Nottingham Biomedical Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, UK
- Martin D. Tobin
- Department of Population Health Sciences, University of Leicester, Leicester, UK
- Moira K.B. Whyte
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
- Ayodeji Adegunsoye
- Department of Medicine, University of Chicago, Chicago, IL, USA
- Naftali Kaminski
- Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA
- Shwu-Fan Ma
- Department of Medicine, University of Virginia, Charlottesville, VA, USA
- Mary E. Strek
- Department of Medicine, University of Chicago, Chicago, IL, USA
- Yingze Zhang
- Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- Tasha E. Fingerlin
- Department of Immunology and Genomic Medicine, National Jewish Health, Denver, CO, USA
- Maria Molina-Molina
- Servei de Pneumologia, Laboratori de Pneumologia Experimental, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain
- Margaret Neighbors
- Genentech, San Francisco, CA, USA
- X. Rebecca Sheng
- Genentech, San Francisco, CA, USA
- Justin M. Oldham
- Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA
- Toby M. Maher
- National Heart and Lung Institute, Imperial College London, London, UK
- Philip L. Molyneaux
- National Heart and Lung Institute, Imperial College London, London, UK
- Carlos Flores
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
- Imre Noth
- Department of Medicine, University of Virginia, Charlottesville, VA, USA
- David A. Schwartz
- Department of Medicine, University of Colorado, Anscuhtz, CO, USA
- Brian L. Yaspan
- Genentech, San Francisco, CA, USA
- R. Gisli Jenkins
- National Heart and Lung Institute, Imperial College London, London, UK
- Louise V. Wain
- Department of Population Health Sciences, University of Leicester, Leicester, UK
- Edward J. Hollox
- Department of Genetics and Genome Biology, University of Leicester, Leicester, UK
- DOI
- https://doi.org/10.1183/23120541.00553-2023
- Journal volume & issue
-
Vol. 10,
no. 1
Abstract
Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF, and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has been reported. Owing to the important role that the human leukocyte antigen (HLA) region plays in the immune response, here we evaluated if HLA genetic variation was associated specifically with IPF risk. Methods We performed a meta-analysis of associations of the HLA region with IPF risk in individuals of European ancestry from seven independent case–control studies of IPF (comprising 5159 cases and 27 459 controls, including a prior study of fibrotic interstitial pneumonia). Single nucleotide polymorphisms, classical HLA alleles and amino acids were analysed and signals meeting a region-wide association threshold of p90% were considered significant. We sought to replicate the previously reported HLA-DQB1 association in the subset of studies independent of the original report. Results The meta-analysis of all seven studies identified four significant independent single nucleotide polymorphisms associated with IPF risk. However, none met the posterior probability for replication criterion. The HLA-DQB1 association was not replicated in the independent IPF studies. Conclusion Variation in the HLA region was not consistently associated with risk in studies of IPF. However, this does not preclude the possibility that other genomic regions linked to the immune response may be involved in the aetiology of IPF.
