title: Genetic determinants of pulmonary fibrosis: evolving concepts.
abstract: Interstitial lung diseases encompass a wide range of diffuse lung disorders that are often complicated by the development of pulmonary fibrosis and that can occur in isolation or in systemic diseases. In the past decade, availability of high-throughput genotyping and large collaborative clinical networks has led to the identification of many genetic variants associated with sporadic and familial fibrotic interstitial pneumonias. Susceptibility to idiopathic pulmonary fibrosis seems to involve a combination of polymorphisms related to epithelial cell injury and dysfunction and abnormal wound healing, whereas chronic inflammation seems important in the development of pulmonary fibrosis in sarcoidosis or collagen vascular diseases such as systemic sclerosis or rheumatoid arthritis; however, each of the disease-associated variants typically has a small effect and they are therefore not helpful in prediction of risk. Genetic studies have substantially expanded understanding of the pathogenesis of pulmonary fibrosis. Future challenges will be to assess how multiple susceptibility alleles interact with each other and environmental factors to determine disease risk and several different phenotypes, to define the mechanism of action and cellular pathways involving susceptibility alleles, and to identify which of the gene products and molecular mechanisms implicated in disease pathobiology are good therapeutic targets.
authors.affiliation: Center for Rare Lung Diseases, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena, Modena, Italy. Electronic address: paolo.spagnolo@unimore.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Spagnolo
authors.affiliation: Respiratory Medicine Unit, Department of Medicine, Solna, Sweden; Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Solna, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Grunewald
authors.affiliation: Imperial College London, London, UK.
authors.forename: Roland M
authors.initials: RM
authors.lastname: du Bois
mesh_terms: D001172:Arthritis, Rheumatoid / Q000150:complications / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics; D009077:Mucins / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000235:genetics*; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics*; D017565:Sarcoidosis, Pulmonary / Q000235:genetics; D012595:Scleroderma, Systemic / Q000150:complications / Q000235:genetics; D019098:Telomerase / Q000235:genetics*
chemical_list: D009077:Mucins; D037721:Pulmonary Surfactant-Associated Protein C; D019098:Telomerase