Georg J Loss1,2, Martin Depner1, Alexander J Hose1, Jon Genuneit3, Anne M Karvonen4, Anne Hyvärinen4, Caroline Roduit5,6, Michael Kabesch7,8, Roger Lauener6,9, Petra Ina Pfefferle10,11, Juha Pekkanen4,12, Jean-Charles Dalphin13, Josef Riedler14,15, Charlotte Braun-Fahrländer16,17, Erika von Mutius1,18, Markus J Ege1,18. 1. 1 Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany. 2. 2 Department of Pediatrics, University of California, San Diego, La Jolla, California. 3. 3 Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany. 4. 4 Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland. 5. 5 Children's Hospital, University of Zürich, Zürich, Switzerland. 6. 6 Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland. 7. 7 Department of Pediatric Pneumology and Allergy, KUNO Children's University Hospital Regensburg, Regensburg, Germany. 8. 8 Clinic for Pediatric Pneumology and Neonatology, Hannover Medical School, Hannover, Germany. 9. 9 Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland. 10. 10 Comprehensive Biomaterial Bank Marburg CBBM, Center for Tumor Biology and Immunology, Faculty of Medicine, Philipp University of Marburg, Marburg, Germany. 11. 11 German Center for Lung Research, Giessen, Germany. 12. 12 Department of Public Health, University of Helsinki, Helsinki, Finland. 13. 13 Department of Respiratory Disease, University of Besançon, University Hospital, Besançon, France. 14. 14 Children's Hospital Schwarzach, Schwarzach, Austria. 15. 15 Teaching Hospital of Paracelsus Private Medical University of Salzburg, Salzburg, Austria. 16. 16 Swiss Tropical and Public Health Institute, Basel, Switzerland. 17. 17 University of Basel, Basel, Switzerland; and. 18. 18 German Center for Lung Research, Comprehensive Pneumology Center Munich, Munich, Germany.
Abstract
RATIONALE: Growing up on a farm protects from childhood asthma and early wheeze. Virus-triggered wheeze in infancy predicts asthma in individuals with a genetic asthma risk associated with chromosome 17q21. OBJECTIVES: To test environmental determinants of infections and wheeze in the first year of life, potential modifications of these associations by 17q21, and the implications for different trajectories of wheeze. METHODS: We followed 983 children in rural areas of Europe from birth until age 6 years. Symptoms of wheeze, rhinitis, fever, and environmental exposures were documented with weekly diaries during year 1. Asthma at age 6 was defined as ever having a reported doctor's diagnosis. Single-nucleotide polymorphisms related to ORMDL3 (rs8076131) and GSDMB (rs7216389, rs2290400) at 17q21 were genotyped. MEASUREMENTS AND MAIN RESULTS: Early wheeze was positively associated with presence of older siblings among carriers of known asthma risk alleles at 17q21 (e.g., rs8076131) (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.16-2.01). Exposure to farm animal sheds was inversely related to wheeze (aOR, 0.44; 95% CI, 0.33-0.60). Both effects were similarly observed in children with transient wheeze up to age 3 years without subsequent development of asthma (aOR, 1.71 [95% CI, 1.09-2.67]; and aOR, 0.48 [95% CI, 0.30-0.76], respectively). CONCLUSIONS: These findings suggest that the chromosome 17q21 locus relates to episodes of acute airway obstruction common to both transient wheeze and asthma. The previously identified asthma risk alleles are the ones susceptible to environmental influences. Thus, this gene-environment interaction reveals two faces of 17q21: The same genotype constitutes genetic risk and allows for environmental protection, thereby providing options for prospective prevention strategies.
RATIONALE: Growing up on a farm protects from childhood asthma and early wheeze. Virus-triggered wheeze in infancy predicts asthma in individuals with a genetic asthma risk associated with chromosome 17q21. OBJECTIVES: To test environmental determinants of infections and wheeze in the first year of life, potential modifications of these associations by 17q21, and the implications for different trajectories of wheeze. METHODS: We followed 983 children in rural areas of Europe from birth until age 6 years. Symptoms of wheeze, rhinitis, fever, and environmental exposures were documented with weekly diaries during year 1. Asthma at age 6 was defined as ever having a reported doctor's diagnosis. Single-nucleotide polymorphisms related to ORMDL3 (rs8076131) and GSDMB (rs7216389, rs2290400) at 17q21 were genotyped. MEASUREMENTS AND MAIN RESULTS: Early wheeze was positively associated with presence of older siblings among carriers of known asthma risk alleles at 17q21 (e.g., rs8076131) (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.16-2.01). Exposure to farm animal sheds was inversely related to wheeze (aOR, 0.44; 95% CI, 0.33-0.60). Both effects were similarly observed in children with transient wheeze up to age 3 years without subsequent development of asthma (aOR, 1.71 [95% CI, 1.09-2.67]; and aOR, 0.48 [95% CI, 0.30-0.76], respectively). CONCLUSIONS: These findings suggest that the chromosome 17q21 locus relates to episodes of acute airway obstruction common to both transient wheeze and asthma. The previously identified asthma risk alleles are the ones susceptible to environmental influences. Thus, this gene-environment interaction reveals two faces of 17q21: The same genotype constitutes genetic risk and allows for environmental protection, thereby providing options for prospective prevention strategies.
Authors: Jennie G Ono; Benjamin I Kim; Yize Zhao; Paul J Christos; Yohannes Tesfaigzi; Tilla S Worgall; Stefan Worgall Journal: J Clin Invest Date: 2020-02-03 Impact factor: 14.808
Authors: Tiffany Ludka-Gaulke; Princy Ghera; Stephen C Waring; Matthew Keifer; Christine Seroogy; James E Gern; Steven Kirkhorn Journal: J Allergy Clin Immunol Date: 2017-09-21 Impact factor: 10.793