Your browser doesn't support javascript.
loading
Heme metabolism genes Downregulated in COPD Cachexia.
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; McDonald, Merry-Lynn N.
Afiliação
  • Wilson AC; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Kumar PL; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Lee S; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Parker MM; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Arora I; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Morrow JD; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Wouters EFM; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Casaburi R; Centre of expertise for chronic organ failure, Horn, the Netherlands.
  • Rennard SI; Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Lomas DA; Department of Medicine, Nebraska Medical Center, Omaha, NE, USA.
  • Agusti A; BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
  • Tal-Singer R; UCL Respiratory, Division of Medicine, University College London, London, UK.
  • Dransfield MT; Fundació Investigació Sanitària Illes Balears (FISIB), Ciber Enfermedades Respiratorias (CIBERES), Barcelona, Catalunya, Spain.
  • Wells JM; Thorax Institute, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.
  • Bhatt SP; GSK R&D, Collegeville, PA, USA.
  • Washko G; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Thannickal VJ; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Tiwari HK; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Hersh CP; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
  • Castaldi PJ; Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Silverman EK; Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
  • McDonald MN; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Respir Res ; 21(1): 100, 2020 May 01.
Article em En | MEDLINE | ID: mdl-32354332
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/m2) and 1/3 criteria: decreased muscle strength (six-minute walk distance < 350 m), anemia (hemoglobin < 12 g/dl), and low fat-free mass index (FFMI) (< 15 kg/m2 among women and < 17 kg/m2 among men) in COPDGene. In ECLIPSE, cachexia was defined as weight-loss > 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. 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.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Caquexia / Doença Pulmonar Obstrutiva Crônica / Heme Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Caquexia / Doença Pulmonar Obstrutiva Crônica / Heme Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article