Altered Expression of Long Noncoding RNAs in Blood after Ischemic Stroke and Proximity to Putative Stroke Risk Loci

Cheryl Dykstra-Aiello, Glen C. Jickling, Bradley Ander, Natasha Shroff, Xinhua Zhan, Da Liu, Heather Hull, Miles Orantia, Boryana Stamova, Frank R Sharp

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Background and Purpose - 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. Methods - 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. Results - 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. Conclusions - 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.

Original languageEnglish (US)
Pages (from-to)2896-2903
Number of pages8
JournalStroke
Volume47
Issue number12
DOIs
StatePublished - Dec 1 2016

Fingerprint

Long Noncoding RNA
Stroke
Transferases
N-Acetylgalactosaminyltransferases
Galactosyltransferases
Lipoprotein(a)
Prostaglandin-Endoperoxide Synthases
Blood Group Antigens
Principal Component Analysis

Keywords

  • gene expression
  • risk factor
  • RNA, long noncoding
  • RNA, untranslated
  • stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

Altered Expression of Long Noncoding RNAs in Blood after Ischemic Stroke and Proximity to Putative Stroke Risk Loci. / Dykstra-Aiello, Cheryl; Jickling, Glen C.; Ander, Bradley; Shroff, Natasha; Zhan, Xinhua; Liu, Da; Hull, Heather; Orantia, Miles; Stamova, Boryana; Sharp, Frank R.

In: Stroke, Vol. 47, No. 12, 01.12.2016, p. 2896-2903.

Research output: Contribution to journalArticle

Dykstra-Aiello, Cheryl ; Jickling, Glen C. ; Ander, Bradley ; Shroff, Natasha ; Zhan, Xinhua ; Liu, Da ; Hull, Heather ; Orantia, Miles ; Stamova, Boryana ; Sharp, Frank R. / Altered Expression of Long Noncoding RNAs in Blood after Ischemic Stroke and Proximity to Putative Stroke Risk Loci. In: Stroke. 2016 ; Vol. 47, No. 12. pp. 2896-2903.
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AU - Jickling, Glen C.

AU - Ander, Bradley

AU - Shroff, Natasha

AU - Zhan, Xinhua

AU - Liu, Da

AU - Hull, Heather

AU - Orantia, Miles

AU - Stamova, Boryana

AU - Sharp, Frank R

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N2 - Background and Purpose - 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. Methods - 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. Results - 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. Conclusions - 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.

AB - Background and Purpose - 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. Methods - 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. Results - 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. Conclusions - 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.

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