title: The Effect of Statins on Blood Gene Expression in COPD.
abstract: BACKGROUND
  COPD is currently the fourth leading cause of death worldwide. Statins are lipid lowering agents with documented cardiovascular benefits. Observational studies have shown that statins may have a beneficial role in COPD. The impact of statins on blood gene expression from COPD patients is largely unknown.
  
  
  OBJECTIVE
  Identify blood gene signature associated with statin use in COPD patients, and the pathways underpinning this signature that could explain any potential benefits in COPD.
  
  
  METHODS
  Whole blood gene expression was measured on 168 statin users and 451 non-users from the ECLIPSE study using the Affymetrix Human Gene 1.1 ST microarray chips. Factor Analysis for Robust Microarray Summarization (FARMS) was used to process the expression data. Differential gene expression analysis was undertaken using the Linear Models for Microarray data (Limma) package adjusting for propensity score and surrogate variables. Similarity of the expression signal with published gene expression profiles was performed in ProfileChaser.
  
  
  RESULTS
  25 genes were differentially expressed between statin users and non-users at an FDR of 10%, including LDLR, CXCR2, SC4MOL, FAM108A1, IFI35, FRYL, ABCG1, MYLIP, and DHCR24. The 25 genes were significantly enriched in cholesterol homeostasis and metabolism pathways. The resulting gene signature showed correlation with Huntington's disease, Parkinson's disease and acute myeloid leukemia gene signatures.
  
  
  CONCLUSIONS
  The blood gene signature of statins' use in COPD patients was enriched in cholesterol homeostasis pathways. Further studies are needed to delineate the role of these pathways in lung biology.
authors.affiliation: The University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Ma'en
authors.initials: M
authors.lastname: Obeidat
authors.affiliation: The University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Nick
authors.initials: N
authors.lastname: Fishbane
authors.affiliation: The University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Prevention of Organ Failure (PROOF) Centre of Excellence, Vancouver, BC, Canada.
authors.forename: Virginia
authors.initials: V
authors.lastname: Chen
authors.affiliation: Prevention of Organ Failure (PROOF) Centre of Excellence, Vancouver, BC, Canada.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hollander
authors.affiliation: The University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada; Prevention of Organ Failure (PROOF) Centre of Excellence, Vancouver, BC, Canada; Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Tebbutt
authors.affiliation: Institut universitaire de cardiologie et de pneumologie de Québec, Department of Molecular Medicine, Laval University, Québec, Canada.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Bossé
authors.affiliation: Prevention of Organ Failure (PROOF) Centre of Excellence, Vancouver, BC, Canada.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Ng
authors.affiliation: Respiratory Therapy Area Unit, GlaxoSmithKline R&D, King of Prussia, Pennsylvania, United States of America.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Miller
authors.affiliation: The University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada; Prevention of Organ Failure (PROOF) Centre of Excellence, Vancouver, BC, Canada.
authors.forename: Bruce
authors.initials: B
authors.lastname: McManus
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rennard
authors.affiliation: The University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada; Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Paré
authors.affiliation: The University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada; Respiratory Division, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
mesh_terms: D000368:Aged; D003710:Demography; D005260:Female; D063990:Gene Ontology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D059467:Transcriptome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors