Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis.
| العنوان: | Association study of human leukocyte antigen (HLA) variants and idiopathic pulmonary fibrosis. |
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| المؤلفون: | Guillen-Guio B; Department of Population Health Sciences, University of Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK., Paynton ML; Department of Population Health Sciences, University of Leicester, UK., Allen RJ; Department of Population Health Sciences, University of Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK., Chin DPW; Department of Population Health Sciences, University of Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK., Donoghue LJ; Genentech, California, USA., Stockwell A; Genentech, California, USA., Leavy OC; Department of Population Health Sciences, University of Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK., Hernandez-Beeftink T; Department of Population Health Sciences, University of Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK., Reynolds C; Imperial College London, London, UK., Cullinan P; Imperial College London, London, UK., Martinez F; Weill Cornell Medicine, New York, USA., Booth HL; University College London Hospitals, London, UK., Fahy WA; GlaxoSmithKline, London, UK., Hall IP; University of Nottingham, Nottingham, UK.; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham, UK., Hart SP; University of Hull, Hull, UK., Hill MR; University of Oxford, Oxford, UK., Hirani N; University of Edinburgh, Edinburgh, UK., Hubbard RB; University of Nottingham, Nottingham, UK.; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham, UK., McAnulty RJ; University College London, London, UK., Millar AB; University of Bristol, Bristol, UK., Navaratnam V; Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.; National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK.; Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane, QLD, Australia., Oballa E; GlaxoSmithKline, London, UK., Parfrey H; Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK., Saini G; University of Nottingham, Nottingham, UK., Sayers I; Centre for Respiratory Research, NIHR Nottingham Biomedical Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, UK., Tobin MD; Department of Population Health Sciences, University of Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK., Whyte MKB; University of Edinburgh, Edinburgh, UK., Adegunsoye A; University of Chicago, Chicago, USA., Kaminski N; Yale School of Medicine, Connecticut, USA., Shwu-Fan M; University of Virginia, Virginia, USA., Strek ME; University of Chicago, Chicago, USA., Zhang Y; University of Pittsburgh, Pittsburgh, USA., Fingerlin TE; National Jewish Health, Colorado, USA., Molina-Molina M; Servei de Pneumologia, Laboratori de Pneumologia Experimental, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain.; Campus de Bellvitge, Universitat de Barcelona, Barcelona, Spain.; Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain., Neighbors M; Genentech, California, USA., Sheng XR; Genentech, California, USA., Oldham JM; University of Michigan, Michigan, USA., Maher TM; National Heart and Lung Institute, Imperial College London, London, UK.; Division of Pulmonary and Critical Care Medicine, University of Southern California, Los Angeles, USA., Molyneaux PL; National Heart and Lung Institute, Imperial College London, London, UK.; Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, UK., Flores C; Centro de Investigacion Biomedica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.; Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.; Genomics Division, Instituto Tecnologico y de Energias Renovables, Santa Cruz de Tenerife, Spain.; Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain., Noth I; University of Virginia, Virginia, USA., Schwartz DA; University of Colorado Medicine, Colorado, USA., Yaspan BL; Genentech, California, USA., Jenkins RG; National Heart and Lung Institute, Imperial College London, London, UK., Wain LV; Department of Population Health Sciences, University of Leicester, UK.; NIHR Leicester Biomedical Research Centre, Leicester, UK., Hollox EJ; Department of Genetics and Genome Biology, University of Leicester, UK. |
| مؤلفون مشاركون: | CleanUP-IPF Investigators of the Pulmonary Trials Cooperative |
| المصدر: | MedRxiv : the preprint server for health sciences [medRxiv] 2023 Jul 24. Date of Electronic Publication: 2023 Jul 24. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | 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. Due 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 a total of 5,159 cases and 27,459 controls, including the 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 p <4.5×10 -4 and a posterior probability of replication >90% 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. Competing Interests: COMPETING INTERESTS LJD, AS, MN, XRS and BLY are full-time employees of Genentech; AS, MN, XRS, and BLY and hold stock options in Roche. JMO reports personal fees from Boehringer Ingelheim, Genentech, United Therapeutics, AmMax Bio and Lupin Pharmaceuticals outside of the submitted work. DAS is the founder and chief scientific officer of Eleven P15, a company focused on the early detection and treatment of pulmonary fibrosis. RGJ reports honoraria from Chiesi, Roche, PatientMPower, AstraZeneca, GSK, Boehringer Ingelheim, and consulting fees from Bristol Myers Squibb, Daewoong, Veracyte, Resolution Therapeutics, RedX, Pliant, Chiesi. LVW reports research funding from GlaxoSmithKline, Roche and Orion Pharma, and consultancy for GlaxoSmithKline and Galapagos, outside of the submitted work. The other authors declare no competing interests. |
| التعليقات: | Update in: ERJ Open Res. 2024 Feb 19;10(1):00553-2023. doi: 10.1183/23120541.00553-2023. (PMID: 38375425) |
| معلومات مُعتمدة: | MC_PC_19004 United Kingdom MRC_ Medical Research Council; K23 HL146942 United States HL NHLBI NIH HHS; R56 HL158935 United States HL NHLBI NIH HHS; United Kingdom WT_ Wellcome Trust; K23 HL138190 United States HL NHLBI NIH HHS |
| تواريخ الأحداث: | Date Created: 20230807 Latest Revision: 20240923 |
| رمز التحديث: | 20240923 |
| مُعرف محوري في PubMed: | PMC10402235 |
| DOI: | 10.1101/2023.07.20.23292940 |
| PMID: | 37546732 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2023.07.20.23292940 |
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