Polymorphism of HDAC9 Gene Is Associated with Increased Risk of Acute Coronary Syndrome in Chinese Han Population

Han, Zhenhua; Dong, Xin; Zhang, Chaoying; Wu, Yue; Yuan, Zuyi; Wang, Xinhong

doi:10.1155/2016/3746276

Cited by 8 publications

(8 citation statements)

References 19 publications

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“…One Asian population-based GWAS identified the following three novel PAD susceptibility loci with genome-wide significance: IPO5/RAP2A (a member of the importin beta family that promotes apolipoprotein A-1 excretion; p = 6.8 × 10 −14 ), EDNRA ( p = 5.3 × 10 −9 ), and HDAC9 ( p = 8.8 × 10 −8 ). For example, the HDAC9 locus was identified in GWAS on stroke, ACS, and PAD [ 64 , 65 ]. HDAC9 increases the risk of disease development by enhancing the atherosclerosis process in large- and small-caliber vessels [ 64 , 65 ].…”

Section: Findings Of Gwas On Variations In Pad-associated Gene Loci Involved In Inflammation Thrombosis and Lipid Imbalancementioning

confidence: 99%

Personalized Cell Therapy for Patients with Peripheral Arterial Diseases in the Context of Genetic Alterations: Artificial Intelligence-Based Responder and Non-Responder Prediction

Salybekov

Wolfien

Kobayashi

et al. 2021

Cells

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Stem/progenitor cell transplantation is a potential novel therapeutic strategy to induce angiogenesis in ischemic tissue, which can prevent major amputation in patients with advanced peripheral artery disease (PAD). Thus, clinicians can use cell therapies worldwide to treat PAD. However, some cell therapy studies did not report beneficial outcomes. Clinical researchers have suggested that classical risk factors and comorbidities may adversely affect the efficacy of cell therapy. Some studies have indicated that the response to stem cell therapy varies among patients, even in those harboring limited risk factors. This suggests the role of undetermined risk factors, including genetic alterations, somatic mutations, and clonal hematopoiesis. Personalized stem cell-based therapy can be developed by analyzing individual risk factors. These approaches must consider several clinical biomarkers and perform studies (such as genome-wide association studies (GWAS)) on disease-related genetic traits and integrate the findings with those of transcriptome-wide association studies (TWAS) and whole-genome sequencing in PAD. Additional unbiased analyses with state-of-the-art computational methods, such as machine learning-based patient stratification, are suited for predictions in clinical investigations. The integration of these complex approaches into a unified analysis procedure for the identification of responders and non-responders before stem cell therapy, which can decrease treatment expenditure, is a major challenge for increasing the efficacy of therapies.

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Section: Findings Of Gwas On Variations In Pad-associated Gene Loci Involved In Inflammation Thrombosis and Lipid Imbalancementioning

confidence: 99%

Personalized Cell Therapy for Patients with Peripheral Arterial Diseases in the Context of Genetic Alterations: Artificial Intelligence-Based Responder and Non-Responder Prediction

Salybekov

Wolfien

Kobayashi

et al. 2021

Cells

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“…It is located on chromosome 7p21.1, 915.4 kb in size and encodes a protein responsible for histone deacetylation [12]. The polymorphisms of HDAC9 gene affect the acetylation and deacetylation processes of histones and thus further cause the activation or inactivation of certain genes [12,13]. The most common polymorphism of the HDAC9 gene is rs2107595, located in the 3′ region of the HDAC9 gene.…”

Section: Introductionmentioning

confidence: 99%

Association between rs2107595 HDAC9 gene polymorphism and advanced carotid atherosclerosis in the Slovenian cohort

Grbić

Gorkič²,

Pleskovič

et al. 2020

Lipids Health Dis

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Background Histone deacetylase 9 (HDAC9) plays an important role in transcriptional regulation, cell cycle progression and developmental events; moreover, it has been investigated as a candidate gene in a number of conditions, including the onset and progression of atherosclerosis. We hypothesized that the rs2107595 HDAC9 gene polymorphism may be associated with advanced carotid artery disease in a Slovenian cohort. We also investigated the effect of this polymorphism on HDAC9 receptor expression in the internal carotid artery (ICA) specimens obtained by endarterectomy. Methods This case-control study enrolled 619 unrelated Slovenian patients: 311 patients with ICA stenosis > 75% as the study group and 308 patients with ICA stenosis < 50% as the control group. Patient laboratory and clinical data were obtained from the medical records. The rs2107595 polymorphisms were genotyped using TaqMan SNP Genotyping assay. HDAC9 expression was assessed by immunohistochemistry in 30 ICA specimens from patients with ICA atherosclerosis > 75%, and the numerical areal density of HDAC9 positive cells was calculated. Results The occurrence of advanced ICA atherosclerosis in the Slovenian cohort was 3.81 times higher in the codominant genetic model (OR = 3.81, 95%CI = 1.06–13.77, p = 0.04), and 3.10 times higher in the recessive genetic model (OR = 3.10, 95%CI = 1.16–8.27, p = 0.02). In addition, the A allele of rs2107595 was associated with increased HDAC9 expression in the ICA specimens obtained by endarterectomy. Conclusions We observed a significant association between the AA genotype of rs2107595 with the advanced carotid artery disease in our Slovenian cohort, indicating that this polymorphism may be a genetic risk factor for ICA atherosclerosis.

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“…For example, HDAC4 is reduced in ischemic stroke model animals and oxygen-glucose deprivation (OGD)-treated neurons, while increased HDAC4 expression reduces infarct volume in ischemic stroke model animals and increases cell viability of OGD-treated neuronal cells [ 9 , 10 , 21 , 22 ]. In addition, HDAC4 has a significant effect on a cognitive function which could be impaired by ischemic stroke [ 23 ]. For example, conditional deletion of HDAC4 leads to learning and memory deficits [ 24 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

HDAC4 in ischemic stroke: mechanisms and therapeutic potential

Kong

Hao

et al. 2018

Clin Epigenet

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Stroke is one of the leading causes of death and disability worldwide, and the majority of the cases are ischemic stroke. However, it still lacks effective treatment except for thrombolytic therapy in an extremely narrow time window. Increased evidence suggests that histone deacetylase 4 (HDAC4) was dysregulated in ischemic stroke, which plays a key role in the pathogenesis of ischemic stroke and post-stroke recovery by affecting neuronal death, angiogenesis, and neurogenesis. Therefore, we aim to review the dysregulation of HDAC4 in ischemic stroke and the role of dysregulated HDAC4 in the pathogenesis of ischemic stroke. Furthermore, the therapeutic potential of modulating HDAC4 in ischemic stroke is discussed.

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Polymorphism of HDAC9 Gene Is Associated with Increased Risk of Acute Coronary Syndrome in Chinese Han Population

Cited by 8 publications

References 19 publications

Personalized Cell Therapy for Patients with Peripheral Arterial Diseases in the Context of Genetic Alterations: Artificial Intelligence-Based Responder and Non-Responder Prediction

Personalized Cell Therapy for Patients with Peripheral Arterial Diseases in the Context of Genetic Alterations: Artificial Intelligence-Based Responder and Non-Responder Prediction

Association between rs2107595 HDAC9 gene polymorphism and advanced carotid atherosclerosis in the Slovenian cohort

HDAC4 in ischemic stroke: mechanisms and therapeutic potential

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