Department of Physiology, Faculty of Medicine, University of Tuzla, Tuzla, Bosnia and Herzegovina.
International Center for Cardiovascular Diseases MC Medicor d.d, Izola, Slovenia.
Lipids Health Dis. 2020 Apr 13;19(1):71. doi: 10.1186/s12944-020-01255-1.
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.
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.
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.
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.
组蛋白去乙酰化酶 9（HDAC9）在转录调控、细胞周期进程和发育事件中发挥重要作用；此外，它已被作为候选基因在多种情况下进行研究，包括动脉粥样硬化的发生和进展。我们假设 rs2107595 HDAC9 基因多态性可能与斯洛文尼亚队列中的颈动脉疾病进展有关。我们还研究了这种多态性对内颈动脉（ICA）标本中 HDAC9 受体表达的影响，这些标本是通过内膜切除术获得的。
这项病例对照研究纳入了 619 名无血缘关系的斯洛文尼亚患者：311 名 ICA 狭窄>75%的患者为研究组，308 名 ICA 狭窄<50%的患者为对照组。从病历中获取患者的实验室和临床数据。使用 TaqMan SNP 基因分型检测法对 rs2107595 多态性进行基因分型。对 30 例 ICA 粥样硬化>75%的患者的 ICA 标本进行 HDAC9 免疫组织化学染色，计算 HDAC9 阳性细胞的数值面积密度。
在斯洛文尼亚队列中，ICA 粥样硬化进展的发生率在共显性遗传模型中高 3.81 倍（OR=3.81，95%CI=1.06-13.77，p=0.04），在隐性遗传模型中高 3.10 倍（OR=3.10，95%CI=1.16-8.27，p=0.02）。此外，rs2107595 的 A 等位基因与内膜切除术后 ICA 标本中 HDAC9 表达增加相关。
我们观察到 rs2107595 的 AA 基因型与我们的斯洛文尼亚队列中的颈动脉疾病进展有显著关联，表明该多态性可能是 ICA 粥样硬化的遗传风险因素。
