title: MUC5B and Idiopathic Pulmonary Fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF), a fatal disease that is a result of complex interactions between genetics and the environment, has limited treatment options. We have identified the MUC5B promoter polymorphism and other common genetic variants that in aggregate explain roughly one-third of disease risk. The MUC5B promoter polymorphism is the strongest and the most replicated genetic risk factor for IPF, appears to be protective and predictive in this disease, and is likely involved in disease pathogenesis through an increase in MUC5B expression in terminal bronchi and honeycombed cysts. Expression of MUC5B is also highly correlated with expression of cilium genes in IPF lung. Our work suggests that mucociliary dysfunction in the distal airway may play a role in the development of progressive fibroproliferative lung disease. In addition, our work has important implications for secondary prevention, early detection, and future early and personalized treatment based on genetic profiles.
authors.affiliation: 1 Department of Medicine, University of Colorado Denver, Aurora, Colorado.|2 Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado.|3 Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado.
authors.forename: Ivana V
authors.initials: IV
authors.lastname: Yang
authors.affiliation: 3 Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado.|4 Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, Colorado; and.
authors.forename: Tasha E
authors.initials: TE
authors.lastname: Fingerlin
authors.affiliation: 1 Department of Medicine, University of Colorado Denver, Aurora, Colorado.|5 Department of Immunology, University of Colorado Denver, Aurora, Colorado.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Evans
authors.affiliation: 1 Department of Medicine, University of Colorado Denver, Aurora, Colorado.
authors.forename: Marvin I
authors.initials: MI
authors.lastname: Schwarz
authors.affiliation: 1 Department of Medicine, University of Colorado Denver, Aurora, Colorado.|3 Center for Genes, Environment, and Health, National Jewish Health, Denver, Colorado.|5 Department of Immunology, University of Colorado Denver, Aurora, Colorado.
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
mesh_terms: D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics*; D008168:Lung / Q000503:physiopathology*; D055257:Mucin-5B / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: C524578:MUC5B protein, human; D055257:Mucin-5B
keywords: MUC5B; gene expression profile; mucociliary dysfunction; pulmonary fibrosis; genetic variant