Altered Expression of Long Noncoding RNAs in Blood After Ischemic Stroke and Proximity to Putative Stroke Risk Loci.
Although peripheral blood mRNA and micro-RNA change after ischemic stroke, any role for long noncoding RNA (lncRNA), which comprise most of the genome and have been implicated in various diseases, is unknown. Thus, we hypothesized that lncRNA expression also changes after stroke.



lncRNA expression was assessed in 266 whole-blood RNA samples drawn once per individual from patients with ischemic stroke and matched with vascular risk factor controls. Differential lncRNA expression was assessed by ANCOVA (P<0.005; fold change>|1.2|), principal components analysis, and hierarchical clustering on a derivation set (n=176) and confirmed on a validation set (n=90). Poststroke temporal lncRNA expression changes were assessed using ANCOVA with confounding factor correction (P<0.005; partial correlation with time since event >|0.4|). Because sexual dimorphism exists in stroke, analyses were performed for each sex separately.



A total of 299 lncRNAs were differentially expressed between stroke and control males, whereas 97 lncRNAs were differentially expressed between stroke and control females. Significant changes of lncRNA expression with time after stroke were detected for 49 lncRNAs in men and 31 lncRNAs in women. Some differentially expressed lncRNAs mapped close to genomic locations of previously identified putative stroke-risk genes, including lipoprotein, lipoprotein(a)-like 2, ABO (transferase A, α1-3-N-acetylgalactosaminyltransferase; transferase B, α1-3-galactosyltransferase) blood group, prostaglandin 12 synthase, and α-adducins.



This study provides evidence of altered and sexually dimorphic lncRNA expression in peripheral blood of patients with stroke compared with that of controls and suggests that lncRNAs have potential for stroke biomarker development. Some regulated lncRNA could regulate some previously identified putative stroke-risk genes.
From the Department of Neurology, University of California at Davis, Sacramento.
Cheryl
C
Dykstra-Aiello
From the Department of Neurology, University of California at Davis, Sacramento.
Glen C
GC
Jickling
From the Department of Neurology, University of California at Davis, Sacramento.
Bradley P
BP
Ander
From the Department of Neurology, University of California at Davis, Sacramento.
Natasha
N
Shroff
From the Department of Neurology, University of California at Davis, Sacramento.
Xinhua
X
Zhan
From the Department of Neurology, University of California at Davis, Sacramento.
DaZhi
D
Liu
From the Department of Neurology, University of California at Davis, Sacramento.
Heather
H
Hull
From the Department of Neurology, University of California at Davis, Sacramento.
Miles
M
Orantia
From the Department of Neurology, University of California at Davis, Sacramento. bsstamova@ucdavis.edu.
Boryana S
BS
Stamova
From the Department of Neurology, University of California at Davis, Sacramento.
Frank R
FR
Sharp
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000097:blood*; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000235:genetics; D013997:Time Factors
D015415:Biomarkers; D062085:RNA, Long Noncoding
RNA, long noncoding; RNA, untranslated; gene expression; risk factor; stroke