Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa

Clinical and Translational Allergy

Anu Laulajainen-Hongisto¹  Annina Lyly²  Tuomas Jartti³  Matti Kankainen⁴  Kishor Dhaygude⁵  Tanzeela Hanif⁵  Risto Renkonen⁶  Pirkko Mattila⁷  Kati Donner⁸  Paula Kauppi⁹  Sanna Toppila-Salmi^1,10  Jean Bousquet^1,11 

[1] Department of Otorhinolaryngology–Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O.Box 263, Kasarmikatu 11-13, 00029 HUS, Helsinki, Finland;Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic;Department of Otorhinolaryngology–Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, P.O.Box 263, Kasarmikatu 11-13, 00029 HUS, Helsinki, Finland;Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland;Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland;HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland;Hematology Research Unit Helsinki, Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland;Translational Immunology Research Program and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland;Haartman Institute, University of Helsinki, Helsinki, Finland;Haartman Institute, University of Helsinki, Helsinki, Finland;HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland;Haartman Institute, University of Helsinki, Helsinki, Finland;Hematology Research Unit Helsinki, Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland;Hematology Research Unit Helsinki, Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland;Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland;Skin and Allergy Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland;Haartman Institute, University of Helsinki, Helsinki, Finland;Université Montpellier, Montpellier, France;MACVIA-France, Montpellier, France;Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Comprehensive Allergy Center, Department of Dermatology and Allergy, Charité–Universitätsmedizin Berlin, Berlin, Germany;

关键词: Asthma;    Allergic rhinitis;    Airway epithelium;    GWAS;    Gene ontology;    Pathway;   

DOI  :  10.1186/s13601-020-00347-6

来源: Springer

【 摘 要 】

Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p < 10–8) with asthma, AR and CRS was created. This yielded a total of 267 significantly asthma/AR–associated loci from 31 GWASs. No significant CRS -associated loci were found in this search. A total of 170 protein coding genes were connected to these loci. Of these, 76/170 (44%) showed bronchial epithelial protein expression in stained microscopic figures of Human Protein Atlas (HPA), and 61/170 (36%) had a literature report of having airway epithelial function. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses were performed, and 19 functional protein categories were found as significantly (p < 0.05) enriched among these genes. These were related to cytokine production, cell activation and adaptive immune response, and all were strongly connected in network analysis. We also identified 15 protein pathways that were significantly (p < 0.05) enriched in these genes, related to T-helper cell differentiation, virus infection, JAK-STAT signaling pathway, and asthma. A third of GWAS-level risk loci genes of asthma or AR seemed to have airway epithelial functions according to our database and literature searches. In addition, many of the risk loci genes were immunity related. Some risk loci genes also related to metabolism, neuro-musculoskeletal or other functions. Functions overlapped and formed a strong network in our pathway analyses and are worth future studies of biomarker and therapeutics.

【 授权许可】

CC BY