Document Type
Article
Journal Title
Respiratory Research
Publication Date
2020
Volume
21
Abstract
INTRODUCTION: Cachexia 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.
METHODS: We 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) (< 20 kg/m
RESULTS: The 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 < 0.05) and ECLIPSE (FDR < 0.05).
DISCUSSION: Several replicated genes regulating heme metabolism were downregulated among participants with COPD cachexia. Impaired heme biosynthesis may contribute to cachexia development through free-iron buildup and oxidative tissue damage.
MeSH Headings
Aged, Aged, 80 and over, Cachexia, Cohort Studies, Down-Regulation, Female, Follow-Up Studies, Genome-Wide Association Study, Heme, Humans, Longitudinal Studies, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive
DOI Link
ISSN
1465-993X
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Wilson, Ava C.; Kumar, Preeti L.; Lee, Sool; Parker, Margaret M.; Arora, Itika; Morrow, Jarrett D.; Wouters, Emiel F.M.; 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.; and McDonald, Merry-Lynn N., "Heme Metabolism Genes Downregulated in COPD Cachexia" (2020). Journal Articles: Pulmonary & Critical Care Med. 30.
https://digitalcommons.unmc.edu/com_pulm_articles/30
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