Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa
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020) 10:45
Clinical and Translational Allergy Open Access
REVIEW
Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa Anu Laulajainen‑Hongisto1,2†, Annina Lyly1,3*† , Tanzeela Hanif4, Kishor Dhaygude4, Matti Kankainen5,6,7, Risto Renkonen4,5, Kati Donner6, Pirkko Mattila4,6, Tuomas Jartti8, Jean Bousquet9,10,11, Paula Kauppi3† and Sanna Toppila‑Salmi3,4†
Abstract 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 G) was a susceptibility locus of asthma and self-reported allergy [41] and, asthma with co-existing hay fever, but not asthma alone [37]. The role of epithelial to mesenchymal transition (EMT) has a critical role in airway remodeling. Human eosinophils co-cultured with bronchial epithelial cells induced EMT, suggestive of their role in airway remodeling, with increased expression of TGFβ1 and SMAD3 phosphorylation in the bronchial epithelial cells [61]. ITGB8 gene encodes Integrin Subunit Beta 8. This protein noncovalently binds to an alpha subunit to form a heterodimeric integrin complex. In general, integrin complexes mediate cell–cell and cell-extracellular matrix interactions and this complex plays a role in human airway epithelial proliferation. High expression levels of
Laulajainen‑Hongisto et al. Clin Transl Allergy
(2020) 10:45
ITGB8 have been associated with high angiogenic and poorly invasive glioblastoma tumors. Inactivation of ITGB8 in the murine airway has been associated with a reduction in IL-1β–induced airway inflammation and fibrosis, which is due to decreased TGF-β activation [62]. Immunity function–related genes
Immunity related SNPs in asthma are mostly in genes linked to HLA region and type 2 inflammation. The region 6p21 (HLA region) is one of the most replicated asthma loci [22]. Several significant SNPs have been associated with class II major histocompatibility antigen (HLA-DR) genes including HLA-DQA1, HLA-DQA2 and HLA-DQB1 [38]. They play a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells, ie. B lymphocytes, dendritic cells and macrophages and are extensively studied because of the association with several autoimmune, infectious and inflammatory diseases [63]. Group-specific Component (GC) gene [also known as Vitamin D-binding protein (VDBP) gene] on chromosome 4q13 and has been found to associate with asthma in children [64]. The rs7041 G-allele was found with increased risk [OR 2.15, CI 95% (1.32–3.50; P = 0.002)] of asthma in codominant, dominant, recessive and allelic models [64]. VDBP carries circulating vitamin D to the target organs, it is a chemotacti
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