Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.atherosclerosis.2017.03.041
Title: Whole blood sequencing reveals circulating microRNA associations with high-risk traits in non-ST-segment elevation acute coronary syndrome
Authors: Wang, Alice
Kwee, Lydia Coulter
Grass, Elizabeth
Neely, Megan L
Gregory, Simon G
Fox, Keith AA
Armstrong, Paul W
White, Harvey D
Ohman, E Magnus
Roe, Matthew T
Shah, Svati H
Chan, Mark Y 
Keywords: Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Peripheral Vascular Disease
Cardiovascular System & Cardiology
Non-STE acute coronary syndrome
High-risk traits
MicroRNA
GLOBAL REGISTRY
CLOPIDOGREL
IMPACT
MIR-28-3P
MORTALITY
PRASUGREL
QUANTIFICATION
CALCIFICATION
THERAPEUTICS
EXPRESSION
Issue Date: 1-Jun-2017
Publisher: ELSEVIER IRELAND LTD
Citation: Wang, Alice, Kwee, Lydia Coulter, Grass, Elizabeth, Neely, Megan L, Gregory, Simon G, Fox, Keith AA, Armstrong, Paul W, White, Harvey D, Ohman, E Magnus, Roe, Matthew T, Shah, Svati H, Chan, Mark Y (2017-06-01). Whole blood sequencing reveals circulating microRNA associations with high-risk traits in non-ST-segment elevation acute coronary syndrome. ATHEROSCLEROSIS 261 : 19-25. ScholarBank@NUS Repository. https://doi.org/10.1016/j.atherosclerosis.2017.03.041
Abstract: Background and aims Although circulating microRNA (miRNAs) have emerged as biomarkers predicting mortality in acute coronary syndrome (ACS), more data are needed to understand these mechanisms. Mapping miRNAs to high-risk traits may identify miRNAs involved in pathways conferring risk for poor outcome in ACS. We aim to investigate the relationship between circulating miRNAs and high-risk traits in non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods Whole-genome miRNA sequencing was performed on RNA extracted from whole blood of 199 patients with NSTE-ACS. Generalized linear models were used to test associations of miRNAs and 13 high-risk clinical traits, including the Global Registry of Acute Coronary Events (GRACE) score, a widely validated risk score for mortality in NSTE-ACS. Results There were 205 nominally significant miRNA-risk factor associations (p < 0.05) observed. Significant associations occurred most frequently with chronic heart failure (HF) (43 miRs), GRACE risk score (30 miRs), and renal function (32 miRs). In hierarchical cluster analysis, chronic HF and GRACE risk score clustered most tightly together, sharing 14 miRNAs with matching fold-change direction. Controlling for a false discovery rate of 5%, chronic HF was significantly associated with lower circulating levels of miR-3135b (p < 0.0006), miR-126-5p (p < 0.0001), miR-142-5p (p = 0.0004) and miR-144-5p (p = 0.0007), while increasing GRACE risk score inversely correlated with levels of miR-3135b (p < 0.0001) and positively correlated with levels of miR-28-3p (p = 0.0002). Conclusions Circulating miRs clustered around two powerful traits for mortality risk in NSTE-ACS. MiR-3135b, which was under-expressed in chronic HF and increasing GRACE risk score, and miR-28-3p, which has no known association with cardiovascular disease, warrant further investigation.
Source Title: ATHEROSCLEROSIS
URI: https://scholarbank.nus.edu.sg/handle/10635/206027
ISSN: 00219150
18791484
DOI: 10.1016/j.atherosclerosis.2017.03.041
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