285
Views
2
CrossRef citations to date
0
Altmetric
Research Articles

Genetic analyses of chr11p15.5 region identify MUC5AC-MUC5B associated with asthma-related phenotypes

, PhDORCID Icon, , MS, , MD, , MD, , MD, , MD, , MD, , MD, , MD, , MD, , MDORCID Icon, , PhD, , MD, , MD, , MD, , MD, , MD, , MD, , PhD & show all
Pages 1824-1835 | Received 30 Jan 2023, Accepted 16 Mar 2023, Published online: 21 Apr 2023

References

  • Rogers DF. Airway mucus hypersecretion in asthma: an undervalued pathology? Curr Opin Pharmacol. 2004;4(3):241–250. doi:10.1016/j.coph.2004.01.011.
  • Thai P, Loukoianov A, Wachi S, Wu R. Regulation of airway mucin gene expression. Annu Rev Physiol. 2008;70:405–429. doi:10.1146/annurev.physiol.70.113006.100441.
  • Lang T, Hansson GC, Samuelsson T. Gel-forming mucins appeared early in metazoan evolution. Proc Natl Acad Sci U S A. 2007;104(41):16209–16214. doi:10.1073/pnas.0705984104.
  • Bonser LR, Erle DJ. Airway mucus and asthma: the role of MUC5AC and MUC5B. J Clin Med. 2017;6:112. doi:10.3390/jcm6120112.
  • Almoguera B, Vazquez L, Mentch F, Connolly J, Pacheco JA, Sundaresan AS, Peissig PL, Linneman JG, McCarty CA, Crosslin D, et al. Identification of four novel loci in asthma in European American and African American populations. Am J Respir Crit Care Med. 2017;195(4):456–463. doi:10.1164/rccm.201604-0861OC.
  • Shrine N, Portelli MA, John C, Soler Artigas M, Bennett N, Hall R, Lewis J, Henry AP, Billington CK, Ahmad A, et al. Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study. Lancet Respir Med. 2019;7(1):20–34. doi:10.1016/S2213-2600(18)30389-8.
  • Ferreira MAR, Mathur R, Vonk JM, Szwajda A, Brumpton B, Granell R, Brew BK, Ullemar V, Lu Y, Jiang Y, BIOS Consortium, et al. Genetic architectures of childhood- and adult-onset asthma are partly distinct. Am J Hum Genet. 2019;104(4):665–684. doi:10.1016/j.ajhg.2019.02.022.
  • Pividori M, Schoettler N, Nicolae DL, Ober C, Im HK. Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: genome-wide and transcriptome-wide studies. Lancet Respir Med. 2019;7(6):509–522. doi:10.1016/S2213-2600(19)30055-4.
  • Han Y, Jia Q, Jahani PS, Hurrell BP, Pan C, Huang P, Gukasyan J, Woodward NC, Eskin E, Gilliland FD, et al. Genome-wide analysis highlights contribution of immune system pathways to the genetic architecture of asthma. Nat Commun. 2020;11(1):1776. doi:10.1038/s41467-020-15649-3.
  • Olafsdottir TA, Theodors F, Bjarnadottir K, Bjornsdottir US, Agustsdottir AB, Stefansson OA, Ivarsdottir EV, Sigurdsson JK, Benonisdottir S, Eyjolfsson GI, et al. Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis. Nat Commun. 2020;11(1):393. doi:10.1038/s41467-019-14144-8.
  • Valette K, Li Z, Bon-Baret V, Chignon A, Bérubé J-C, Eslami A, Lamothe J, Gaudreault N, Joubert P, Obeidat M, et al. Prioritization of candidate causal genes for asthma in susceptibility loci derived from UK Biobank. Commun Biol. 2021;4(1):700. doi:10.1038/s42003-021-02227-6.
  • Demenais F, Margaritte-Jeannin P, Barnes KC, Cookson WOC, Altmüller J, Ang W, Barr RG, Beaty TH, Becker AB, Beilby J, Australian Asthma Genetics Consortium (AAGC) collaborators, et al. Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks. Nat Genet. 2018;50(1):42–53. doi:10.1038/s41588-017-0014-7.
  • Fingerlin TE, Murphy E, Zhang W, Peljto AL, Brown KK, Steele MP, Loyd JE, Cosgrove GP, Lynch D, Groshong S, et al. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet. 2013;45(6):613–620. doi:10.1038/ng.2609.
  • Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, Fingerlin TE, Zhang W, Gudmundsson G, Groshong SD, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011;364(16):1503–1512. doi:10.1056/NEJMoa1013660.
  • Allen RJ, Porte J, Braybrooke R, Flores C, Fingerlin TE, Oldham JM, Guillen-Guio B, Ma S-F, Okamoto T, John AE, et al. Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study. Lancet Respir Med. 2017;5(11):869–880. doi:10.1016/S2213-2600(17)30387-9.
  • Noth I, Zhang Y, Ma S-F, Flores C, Barber M, Huang Y, Broderick SM, Wade MS, Hysi P, Scuirba J, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Lancet Respir Med. 2013;1(4):309–317. doi:10.1016/S2213-2600(13)70045-6.
  • Allen RJ, Guillen-Guio B, Oldham JM, Ma S-F, Dressen A, Paynton ML, Kraven LM, Obeidat M, Li X, Ng M, et al. Genome-wide association study of susceptibility to idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2020;201(5):564–574. doi:10.1164/rccm.201905-1017OC.
  • Hobbs BD, Putman RK, Araki T, Nishino M, Gudmundsson G, Gudnason V, et al. Overlap of genetic risk between interstitial lung abnormalities and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2019;200:1402–1413.
  • Sakaue S, Kanai M, Tanigawa Y, Karjalainen J, Kurki M, Koshiba S, et al. A cross-population atlas of genetic associations for 220 human phenotypes. Nat Genet. 2021;53:1415–1424.
  • Travis WD, Costabel U, Hansell DM, King TE, Lynch DA, Nicholson AG, Ryerson CJ, Ryu JH, Selman M, Wells AU, ATS/ERS Committee on Idiopathic Interstitial Pneumonias, et al. An official American Thoracic Society/European Respiratory Society statement: update of the international multidisciplinary classification of the idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188(6):733–748.
  • Buniello A, MacArthur JAL, Cerezo M, Harris LW, Hayhurst J, Malangone C, et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucl Acids Res. 2019;47:D1005–D1012.
  • GTEx Consortium Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science. 2015;348:648–660.
  • Moore WC, Bleecker ER, Curran-Everett D, Erzurum SC, Ameredes BT, Bacharier L, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol. 2007;119:405–413.
  • Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. 2010;181:315–323.
  • Jarjour NN, Erzurum SC, Bleecker ER, Calhoun WJ, Castro M, Comhair SA, et al. Severe asthma: lessons learned from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. Am J Respir Crit Care Med. 2012;185:356–362.
  • Denlinger LC, Phillips BR, Ramratnam S, Ross K, Bhakta NR, Cardet JC, et al. Inflammatory and comorbid features of patients with severe asthma and frequent exacerbations. Am J Respir Crit Care Med. 2017;195:302–313.
  • Teague WG, Phillips BR, Fahy JV, Wenzel SE, Fitzpatrick AM, Moore WC, et al. Baseline features of the severe asthma research program (SARP III) cohort: differences with age. J Allergy Clin Immunol Pract. 2018;6:545–554.
  • Li X, Hastie AT, Peters MC, Hawkins GA, Phipatanakul W, Li H, et al. Investigation of the relationship between IL-6 and type 2 biomarkers in patients with severe asthma. J Allergy Clin Immunol. 2020;145:430–433.
  • Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, Maller J, Sklar P, de Bakker PIW, Daly MJ, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–575.
  • Li X, Ampleford EJ, Howard TD, Moore WC, Torgerson DG, Li H, et al. Genome-wide association studies of asthma indicate opposite immunopathogenesis direction from autoimmune diseases. J Allergy Clin Immunol. 2012;130:861–868.
  • Li X, Christenson SA, Modena B, Li H, Busse WW, Castro M, et al. Genetic analyses identify GSDMB associated with asthma severity, exacerbations, and antiviral pathways. J Allergy Clin Immunol. 2021;147:894–909.
  • Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–265.
  • Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29:15–21.
  • Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.
  • Kasela S, Ortega V, Martorella M, Garudadri S, Nguyen J, Ampleford E, et al. Genetic and non-genetic factors affecting the expression of COVID-19 relevant genes in SPIROMICS bronchial epithelium. Genome Med. 2021;13:66.
  • Li X, Hawkins GA, Moore WC, Hastie AT, Ampleford EJ, Milosevic J, et al. Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort. J Asthma. 2016;53:775–782.
  • Li X, Hastie AT, Hawkins GA, Moore WC, Ampleford EJ, Milosevic J, et al. eQTL of bronchial epithelial cells and bronchial alveolar lavage deciphers GWAS-identified asthma genes. Allergy. 2015;70:1309–1318.
  • Lachowicz-Scroggins ME, Yuan S, Kerr SC, Dunican EM, Yu M, Carrington SD, et al. Abnormalities in MUC5AC and MUC5B Protein in Airway Mucus in Asthma. Am J Respir Crit Care Med. 2016;194:1296–1299.
  • Welsh KG, Rousseau K, Fisher G, Bonser LR, Bradding P, Brightling CE, et al. MUC5AC and a glycosylated variant of MUC5B alter mucin composition in children with acute asthma. Chest. 2017;152:771–779.
  • Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009;180:388–395.
  • Dunican EM, Elicker BM, Gierada DS, Nagle SK, Schiebler ML, Newell JD, et al. Mucus plugs in patients with asthma linked to eosinophilia and airflow obstruction. J Clin Invest. 2018;128:997–1009.
  • Li X, Hawkins GA, Ampleford EJ, Moore WC, Li H, Hastie AT, Howard TD, Boushey HA, Busse WW, Calhoun WJ, et al. Genome-wide association study identifies TH1 pathway genes associated with lung function in asthmatic patients. J Allergy Clin Immunol. 2013;132(2):313–320.e15.
  • Henke MO, Renner A, Huber RM, Seeds MC, Rubin BK. MUC5AC and MUC5B mucins are decreased in cystic fibrosis airway secretions. Am J Respir Cell Mol Biol. 2004;31:86–91.
  • Kim DH, Chu HS, Lee JY, Hwang SJ, Lee SH, Lee HM. Up-regulation of MUC5AC and MUC5B mucin genes in chronic rhinosinusitis. Arch Otolaryngol Head Neck Surg. 2004;130:747–752.
  • Radicioni G, Ceppe A, Ford AA, Alexis NE, Barr RG, Bleecker ER, et al. Airway mucin MUC5AC and MUC5B concentrations and the initiation and progression of chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2021;9:1241–1254.
  • Kesimer M, Ford AA, Ceppe A, Radicioni G, Cao R, Davis CW, Doerschuk CM, Alexis NE, Anderson WH, Henderson AG, et al. Airway mucin concentration as a marker of chronic bronchitis. N Engl J Med. 2017;377(10):911–922.
  • Roy MG, Livraghi-Butrico A, Fletcher AA, McElwee MM, Evans SE, Boerner RM, Alexander SN, Bellinghausen LK, Song AS, Petrova YM, et al. Muc5b is required for airway defence. Nature. 2014;505(7483):412–416.
  • Dickey BF, Whitsett JA. Understanding interstitial lung disease: it’s in the mucus. Am J Respir Cell Mol Biol. 2017;57:12–14.
  • Evans CM, Raclawska DS, Ttofali F, Liptzin DR, Fletcher AA, Harper DN, et al. The polymeric mucin Muc5ac is required for allergic airway hyperreactivity. Nat Commun. 2015;6:6281.
  • Bonser LR, Zlock L, Finkbeiner W, Erle DJ. Epithelial tethering of MUC5AC-rich mucus impairs mucociliary transport in asthma. J Clin Invest. 2016;126:2367–2371.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.