YKL-40 as a clinical biomarker in adult patients with CF: Implications of a CHI3L1 single nucleotide polymorphism in disease severity |
| |
| Institution: | 1. Institut de Recherches Cliniques de Montréal (IRCM), 110 Avenue des Pins Ouest, Montréal, Québec, H2W 1R7, Canada;2. Unité de Recherche Clinique Appliquée, CHU Ste-Justine, 3175 Côte-Sainte-Catherine, Montréal, Québec, H3T 1C5, Canada;3. Université de Montréal, Department of Medicine, 2900, Boul. Édouard-Montpetit Montréal, Québec, H3T 1J4, Canada;1. Department of Paediatric Respiratory Medicine, Royal Brompton Hospital and National Heart Lung Institute Imperial College London, UK;2. UCL Great Ormond Street Institute of Child Health, and Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK;3. Bristol Royal Hospital for Children, Bristol, UK;4. Stanford School of Law, USA;5. Clinical Trials Accelerator Platform, Cystic Fibrosis Trust, UK;6. Cystic Fibrosis Trust, UK;7. UK CF Registry, Cystic Fibrosis Trust and Department of Paediatric Respiratory Medicine, Royal Brompton Hospital and National Heart Lung Institute, Imperial College London, UK;8. Department of Adult Cystic Fibrosis, Royal Brompton Hospital and National Heart Lung Institute Imperial College London;1. National Heart Lung Institute, Imperial College London, London, United Kingdom;2. Department of Paediatric Respiratory Medicine, Royal Brompton and Harefield Trust, London, United Kingdom;3. School of Medicine, Dentistry and Biomedical Sciences, Queen''s University, Belfast, United Kingdom;4. Department of Adult Cystic Fibrosis, Royal Brompton and Harefield Trust, London, United Kingdom;5. Clinical Trials Accelerator Platform, Cystic Fibrosis Trust, United Kingdom;6. RTI Health Solutions, Health Preference Assessment, Belfast, United Kingdom;7. Queen Elizabeth Hospital, Birmingham, United Kingdom;1. Respiratory and Sleep Medicine, Royal Children''s Hospital, Melbourne, Australia;2. Respiratory, Murdoch Children''s Research Institute, Melbourne, Australia;3. Department of Paediatrics, University of Melbourne, Melbourne, Australia;4. Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia;5. Division of Paediatrics and Child Health, Faculty of Medicine, The University of Western Australia, Perth, Australia;6. Department of Respiratory Medicine and Sleep Medicine, Perth Children''s Hospital, Perth, Australia;1. Department of Translational Research NTMS, University of Pisa Medical School, Pisa, Italy;2. Department of Pathology, University of Pisa Medical School, Pisa, Italy;3. Children''s Hospital, Ludwig-Maximilians-University Munich, German Center for Lung Research (DZL), Munich, Germany;4. University of Tübingen Children''s Hospital, Section of Pediatric Infectiology and Immunology, Tübingen, Germany;5. Department of Medicine, General Pathology Division, University of Verona, Verona, Italy;1. Wal-yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, Nedlands, Australia;2. Department of Pediatrics, Pediatric Pulmonary Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;3. Department of Respiratory and Sleep Medicine, Perth Children''s Hospital, Nedlands, Australia;4. Faculty of Health and Medical Sciences, University of Western Australia, Nedlands, Australia;5. Department of Pediatrics, Emory University School of Medicine, Atlanta, United States;6. Center for CF & Airways Disease Research, Children''s Healthcare of Atlanta, Atlanta, United States;7. Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Subiaco, Australia;8. Occupation and Environment, School of Public Health, Curtin University, Bentley, Australia;9. Department of Respiratory Medicine, Royal Children''s Hospital, Parkville, Australia;10. Murdoch Childrens Research Institute, Parkville, Australia;11. Department of Paediatrics, University of Melbourne, Parkville, Australia;1. University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam;2. School of Business and Economics, NUI Galway, Galway, Ireland;3. Professor of Health Economics, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences Queens University Belfast, UK |
| |
| Abstract: | BackgroundYKL-40 (chitinase 3-like 1 gene; CHI3L1) is an inflammatory marker that is increased in the blood of patients with inflammatory diseases, including cystic fibrosis (CF). The objective of our study was to explore the relationship between circulating levels of YKL-40, selected CHI3L1 single nucleotide polymorphisms (SNPs) and the severity of CF disease.MethodsA prospective cohort of 188 adult patients with CF was established in 2015. Blood samples and clinical data were collected over 2 years to analyze the circulating levels of YKL-40 and to genotype selected CHI3L1 SNPs. We also looked for an association between these factors and clinical parameters.ResultsWe found that according to the serum YKL-40 concentration, the patients could be categorized into two distinct groups: low and high YKL-40. Compared to the patients in the low YKL-40 group, the patients in the high YKL-40 group had lower lung function (P < 0.001), a higher proportion of delF508 homozygote mutations (P= 0.027) and dysglycemia (P= 0.015). They were also more colonized with Pseudomonas aeruginosa (P= 0.003) and required more frequent antibiotic intravenous courses (P < 0.001). We also observed that patients expressing the C/C-rs4950928 genotype had higher levels of YKL-40 in their blood and were more frequently dysglycemic.ConclusionOur study suggests that YKL-40 could be a potential biomarker of CF disease severity. Furthermore, the CHI3L1 rs4950928 SNP could be a susceptible gene that could be used by CF health professionals to identify patients who are the most at risk of having a severe clinical profile. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
