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Thromb Haemost 2021; 121(03): 396-404
DOI: 10.1055/s-0040-1717116
Atherosclerosis and Ischaemic Disease

Interactive Effects of a Combination of the HDAC3 and HDAC9 Genes with Diabetes Mellitus on the Risk of Ischemic Stroke

Hung-Yi Chiou
1   School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan
2   Master Program in Applied Molecular Epidemiology, College of Public Health, Taipei Medical University, Taipei, Taiwan
,
Chyi-Huey Bai 
1   School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan
,
Li-Ming Lien
3   School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
4   Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
,
Chaur-Jong Hu
3   School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
5   Stroke Center, Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
,
Jiann-Shing Jeng
6   Stroke Center and Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
,
Sung-Chun Tang
6   Stroke Center and Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan
,
Huey-Juan Lin
7   Department of Emergency Medicine, Chi-Mei Medical Center, Tainan, Taiwan
8   Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan
,
Yi-Chen Hsieh
2   Master Program in Applied Molecular Epidemiology, College of Public Health, Taipei Medical University, Taipei, Taiwan
9   PhD Program of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
10   PhD Program in Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipei, Taiwan
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Abstract

Background and Aim Previous studies indicated that the HDAC3 and HDAC9 genes play critical roles in atherosclerosis and ischemic stroke (IS). The purpose of this study was to investigate the association of combined single-nucleotide polymorphisms in the HDAC3 and HDAC9 genes with the susceptibility to IS.

Methods A case–control study was conducted including 863 IS patients and 863 age- and gender-matched healthy participants. A polygenic score was developed to estimate the contribution of a combination of the HDAC3 and HDAC9 genes to the risk of IS. The interactive effects of traditional risk factors of stroke and the polygenic score on the risk of IS were explored. Additionally, the association between the polygenic score and the progression of atherosclerosis, a potential risk factor of IS, was examined in our healthy controls.

Results Subjects with a higher polygenic score had an increased risk of IS (odds ratio: 1.83; 95% confidence interval: 1.38–2.43) after adjusting for covariates compared with individuals with a lower polygenic score. An interactive effect of diabetes mellitus and the polygenic score on the risk of IS was observed. A significant positive correlation between the polygenic score and a change in the plaque score (standardized β = 0.42, p = 0.0235) in healthy controls with diabetes mellitus was found.

Conclusion Our results suggested that the combination of the HDAC3 and HDAC9 genes with a history of diabetes mellitus could exacerbate the deterioration of atherosclerosis, thereby increasing the risk of IS. Further studies are warranted to explore our results in other populations.

Keywords

ischemic stroke - atherosclerosis - HDAC3 - HDAC9 - single-nucleotide polymorphism

Authors' Contributions

H.-Y.C. and C.-H.B. conceived and designed the experiments. H.-Y.C. performed the experiments. H.-Y.C. and C.-H.B. analyzed the data. L.-M.L., C-.J.H., J.-S.J, S.-C.T, and H-.J.L. recruited study subjects. H.-Y.C. wrote the paper. All authors read and approved the final manuscript.


Supplementary Material



Publication History

Received: 03 June 2020

Accepted: 22 August 2020

Article published online:
22 September 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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