학술논문
Heme metabolism genes Downregulated in COPD Cachexia
Document Type
article
Author
Wilson, Ava C; Kumar, Preeti L; Lee, Sool; Parker, Margaret M; Arora, Itika; Morrow, Jarrett D; Wouters, Emiel FM; Casaburi, Richard; Rennard, Stephen I; Lomas, David A; Agusti, Alvar; Tal-Singer, Ruth; Dransfield, Mark T; Wells, J Michael; Bhatt, Surya P; Washko, George; Thannickal, Victor J; Tiwari, Hemant K; Hersh, Craig P; Castaldi, Peter J; Silverman, Edwin K; McDonald, Merry-Lynn N
Source
Respiratory Research. 21(1)
Subject
Language
Abstract
IntroductionCachexia contributes to increased mortality and reduced quality of life in Chronic Obstructive Pulmonary Disease (COPD) and may be associated with underlying gene expression changes. Our goal was to identify differential gene expression signatures associated with COPD cachexia in current and former smokers.MethodsWe analyzed whole-blood gene expression data from participants with COPD in a discovery cohort (COPDGene, N = 400) and assessed replication (ECLIPSE, N = 114). To approximate the consensus definition using available criteria, cachexia was defined as weight-loss > 5% in the past 12 months or low body mass index (BMI) ( 5% in the past 12 months or low BMI and 3/5 criteria: decreased muscle strength, anorexia, abnormal biochemistry (anemia or high c-reactive protein (> 5 mg/l)), fatigue, and low FFMI. Differential gene expression was assessed between cachectic and non-cachectic subjects, adjusting for age, sex, white blood cell counts, and technical covariates. Gene set enrichment analysis was performed using MSigDB.ResultsThe prevalence of COPD cachexia was 13.7% in COPDGene and 7.9% in ECLIPSE. Fourteen genes were differentially downregulated in cachectic versus non-cachectic COPD patients in COPDGene (FDR