TheMUC5Bpromoter polymorphism is associated with specific interstitial lung abnormality subtypes
Year: 2017
Type: article
Study design: Observational Study
Abstract: TheMUC5Bpromoter polymorphism (rs35705950) has been associated with interstitial lung abnormalities (ILA) in white participants from the general population; whether these findings are replicated and influenced by the ILA subtype is not known. We evaluated the associations between theMUC5Bgenotype and ILA in cohorts with extensive imaging characterisation. We performed ILA phenotyping andMUC5Bpromoter genotyping in 5308 and 9292 participants from the AGES-Reykjavik and COPDGene cohorts, respectively. We found that ILA was present in 7% of participants from the AGES-Reykjavik, 8% of non-Hispanic white participants from COPDGene and 7% of African-American participants from COPDGene. Although theMUC5Bgenotype was strongly associated (after correction for multiple testing) with ILA (OR 2.1, 95% CI 1.8–2.4, p=1×10−26), there was evidence of significant heterogeneity between cohorts (I2=81%). When narrowed to specific radiologic subtypes, (e.g.subpleural ILA), theMUC5Bgenotype remained strongly associated (OR 2.6, 95% CI 2.2–3.1, p=1×10−30) with minimal heterogeneity (I2=0%). Although there was no evidence that theMUC5Bgenotype influenced survival, there was evidence thatMUC5Bgenotype improved risk prediction for possible usual interstitial pneumonia (UIP) or a UIP pattern in non-Hispanic white populations. TheMUC5Bpromoter polymorphism is strongly associated with ILA and specific radiologic subtypes of ILA, with varying degrees of heterogeneity in the underlying populations.
Source: European Respiratory Journal
Authors: Rachel K. Putman, Gunnar Gudmundsson, Tetsuro Araki, Mizuki Nishino, Sigurdur Sigurdsson, Elías F. Gudmundsson, Gudny Eiríksdottír, Thor Aspelund, James C. Ross, Raúl San José Estépar, Ezra R. Miller, Yoshitake Yamada, Masahiro Yanagawa, Noriyuki Tomiyama, Lenore J. Launer, Tamara B. Harris, Souheil El-Chemaly, Benjamin A. Raby, Michael H. Cho, Ivan O. Rosas, George R. Washko, David A. Schwartz, Edwin K. Silverman, Vilmundur Gudnason, Hiroto Hatabu, Gary M. Hunninghake
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Role of Genetics in Idiopathic Pulmonary Fibrosis (IPF), THE AGES STUDY - THE REYKJAVIK STUDY OF HEALTHY AGING FOR THE NEW MILLENUM, G1702080553, Functional Genomic Approaches to Dissect COPD GWAS Loci, Identifying Genetic Determinants of Severe, Early-Onset COPD, The Functional Consequences of the 17q12 Asthma Susceptibility Locus, G230712557, G250924255, G2823985716, G3336302228, G3351002399, G3360363946, G3402222819, Systems Biology of Airway Disease, G3588125056, Integrative Genomics of Acute Asthma Control, Lymphatics and Lung Allograft Rejection, (2 of 2) Genetic Epidemiology of COPD, CT Volume Measurement of Lung Cancer treated with Erlotinib: Genomic Correlation, The clinical impact of longitudinal measures of cardiac and pulmonary vascular morphology in smokers, Interstitial Lung Abnormalities: Defining the Phenotype, Causes, and Consequences., CT-based Phenotype for Airway Remodeling in COPD based on Airway Wall Density, Machine Learning Development for Subtyping COPD, (1 of 2) Genetic Epidemiology of COPD, (2 of 2) Genetic Epidemiology of COPD, MUC5B, a novel therapeutic target for Idiopathic Pulmonary Fibrosis (IPF), G6316995398, Functional Genetics in Idiopathic Pulmonary Fibrosis, G6737287751, Mechanisms of Familial Pulmonary Fibrosis, Clinical and Molecular Profiles of Smokers with Subclinical Interstitial Lung Disease, G7373387228, Skeletal muscle, subcutaneous fat, and clinical outcomes in smokers, G8937322086, G8956324075, G9000049958, G9000091268, G9000124518, G9000228787, G9000339644, Clinical Genetics and Screening for Pulmonary Fibrosis, Pathophysiologic and Therapeutic Mechanisms of Aspirin Exacerbated Respiratory Disease, Colorado Undergraduate Research in Environmental Health Sciences, Integrated Training in Respiratory Research, Distinct and Overlapping Pathways of Fibrosis and Emphysema in Cigarette Smokers, Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung Abnormalities
OpenAlex ID: W2754180290