Association Between the MUC5B Promoter Polymorphism and Survival in Patients With Idiopathic Pulmonary Fibrosis

作者：Anna L. Peljto, Yingze Zhang, Tasha E. Fingerlin, Shwu‐Fan Ma, Joe G. N. Garcia, Thomas J. Richards, Lori J. Silveira, Kathleen O. Lindell, Mark P. Steele, James E. Loyd, Kevin F. Gibson, Max A. Seibold, Kevin K. Brown, Janet L. Talbert, Cheryl R. Markin, Karl Kossen, Scott D. Seiwert, Elissa Murphy, Imre Noth, Marvin I. Schwarz, Naftali Kaminski, David A. Schwartz · 发表于：JAMA · 年份：2013 · DOI：10.1001/jama.2013.5827 · 被引用次数：457 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Cystic Fibrosis Research Advances、Systemic Sclerosis and Related Diseases

IMPORTANCE: Current prediction models of mortality in idiopathic pulmonary fibrosis (IPF), which are based on clinical and physiological parameters, have modest value in predicting which patients will progress. In addition to the potential for improving prognostic models, identifying genetic and molecular features that are associated with IPF mortality may provide insight into the underlying mechanisms of disease and inform clinical trials. OBJECTIVE: To determine whether the MUC5B promoter polymorphism (rs35705950), previously reported to be associated with the development of pulmonary fibrosis, is associated with survival in IPF. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of survival in 2 independent cohorts of patients with IPF: the INSPIRE cohort, consisting of patients enrolled in the interferon-γ1b trial (n = 438; December 15, 2003-May 2, 2009; 81 centers in 7 European countries, the United States, and Canada), and the Chicago cohort, consisting of IPF participants recruited from the Interstitial Lung Disease Clinic at the University of Chicago (n = 148; 2007-2010). The INSPIRE cohort was used to model the association of the MUC5B genotype with survival, accounting for the effect of matrix metalloproteinase 7 (MMP-7) blood concentration and other demographic and clinical covariates. The Chicago cohort was used for replication of findings. MAIN OUTCOMES AND MEASURES: The primary end point was all-cause mortality. RESULTS: The numbers of patients in the GG, GT...