Abstract
BackgroundCOPD 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.ObjectiveIdentify blood gene signature associated with statin use in COPD patients, and the pathways underpinning this signature that could explain any potential benefits in COPD.MethodsWhole 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.Results25 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.ConclusionThe 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.
Highlights
Chronic obstructive pulmonary disease (COPD) is characterized by chronic irreversible airflow limitation that is often accompanied by systemic inflammation and comorbidities [1,2]
25 genes were differentially expressed between statin users and non-users at an false discovery rate (FDR) of 10%, including low-density lipoprotein receptor (LDLR), CXCR2, sterol-C4-methyl oxidase-like (SC4MOL), FAM108A1, IFI35, FRYL, ATP-binding cassette sub-family G member 1 (ABCG1), Myosin regulatory light chain interacting protein (MYLIP), and DHCR24
Associations in the opposite direction were reported in the Multi- Ethnic Study of Atherosclerosis (MESA) study, in which HDL levels were negatively associated with FEV1/FVC ratio and percent emphysema [15]
Summary
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
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