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HDAC9 Polymorphism Alters Blood Gene Expression in Patients with Large Vessel Atherosclerotic Stroke

  • Natasha Shroff
  • Bradley P. Ander
  • Xinhua Zhan
  • Boryana Stamova
  • DaZhi Liu
  • Heather Hull
  • Farah R. Hamade
  • Cheryl Dykstra-Aiello
  • Kwan Ng
  • Frank R. Sharp
  • Glen C. Jickling
Original Article
  • 48 Downloads

Abstract

The histone deacetylase 9 (HDAC9) polymorphism rs2107595 is associated with an increased risk for large vessel atherosclerotic stroke (LVAS). In humans, there remains a need to better understand this HDAC9 polymorphism’s contribution to large vessel stroke. In this pilot study, we evaluated whether the HDAC9 polymorphism rs2107595 is associated with differences in leukocyte gene expression in patients with LVAS. HDAC9 SNP rs2107595 was genotyped in 155 patients (43 LVAS and 112 vascular risk factor controls). RNA isolated from blood was processed on whole genome microarrays. Gene expression was compared between HDAC9 risk allele-positive and risk allele-negative LVAS patients and controls. Functional analysis identified canonical pathways and molecular functions associated with rs2107595 in LVAS. In HDAC9 SNP rs2107595 risk allele-positive LVAS patients, there were 155 genes differentially expressed compared to risk allele-negative patients (fold change > |1.2|, p < 0.05). The 155 genes separated the risk allele-positive and risk allele-negative LVAS patients on a principal component analysis. Pathways associated with HDAC9 risk allele-positive status involved IL-6 signaling, cholesterol efflux, and platelet aggregation. These preliminary data suggest an association with the HDAC9 rs2107595 risk allele and peripheral immune, lipid, and clotting systems in LVAS. Further study is required to evaluate whether these differences are related to large vessel atherosclerosis and stroke risk.

Keywords

SNP Polymorphism Gene expression Large vessel stroke Ischemic stroke Atherosclerosis 

Notes

Funding Information

This study was completed with funds from the American Heart Association (GCJ) and the National Institutes of Health (FRS, BS, GCJ: NS075035, NS079153, NS097000).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All patients or their surrogates provided informed consent for this study.

Supplementary material

12975_2018_619_MOESM1_ESM.docx (15 kb)
ESM 1 (DOCX 14.9 kb)
12975_2018_619_MOESM2_ESM.docx (29 kb)
ESM 2 (DOCX 28.6 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Natasha Shroff
    • 1
    • 2
  • Bradley P. Ander
    • 1
  • Xinhua Zhan
    • 1
  • Boryana Stamova
    • 1
  • DaZhi Liu
    • 1
  • Heather Hull
    • 1
  • Farah R. Hamade
    • 1
  • Cheryl Dykstra-Aiello
    • 1
  • Kwan Ng
    • 1
  • Frank R. Sharp
    • 1
  • Glen C. Jickling
    • 1
  1. 1.Department of NeurologyUniversity of California at Davis School of MedicineSacramentoUSA
  2. 2.MIND Institute Wet LabsSacramentoUSA

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