TY - JOUR
T1 - The effect of statins on blood gene expression in COPD
AU - Obeidat, Ma'en
AU - Fishbane, Nick
AU - Nie, Yunlong
AU - Chen, Virginia
AU - Hollander, Zsuzsanna
AU - Tebbutt, Scott J.
AU - Bossé, Yohan
AU - Ng, Raymond T.
AU - Miller, Bruce E.
AU - McManus, Bruce
AU - Rennard, Stephen
AU - Paré, Peter D.
AU - Sin, Don D.
N1 - Funding Information:
BEM is an employee and shareholder of GSK. SR has served as a consultant, participated in advisory boards, received honorarium for speaking or grant support from: American Board of Internal Medicine, Advantage Healthcare, Almirall, American Thoracic Society, AstraZeneca, Baxter, Boehringer Ingelheim, Chiesi, ClearView Healthcare, Cleveland Clinic, Complete Medical Group, CSL, Dailchi Sankyo, Decision Resources, Forest, Gerson Lehman, Grifols, GroupH, Guidepoint Global, Haymarket, Huron Consulting, Inthought, Johnson and Johnson, Methodist Health System – Dallas, NCI Consulting, Novartis, Pearl, Penn Technology, Pfizer, PlanningShop, PSL FirstWord, Qwessential, Takeda, Theron and WebMD. Since August 10, 2015 he as served as chief clinical scientist, new clinical development, AstraZeneca, UK. DDS: Over the past 3 years, DDS has served as a consultant on AstraZeneca (AZ) and Novartis Advisory Boards for COPD. He has been a consultant with Amgen and Almirall. He has received research funding from AZ and Boehringer Ingelheim (BI). He has given lectures sponsored by BI and AZ. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.
Publisher Copyright:
© 2015 Obeidat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/10/13
Y1 - 2015/10/13
N2 - 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. Conclusion 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.
AB - 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. Conclusion 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.
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U2 - 10.1371/journal.pone.0140022
DO - 10.1371/journal.pone.0140022
M3 - Article
C2 - 26462087
AN - SCOPUS:84949035652
SN - 1932-6203
VL - 10
JO - PLoS One
JF - PLoS One
IS - 10
M1 - e0140022
ER -