Petrovič David, Letonja Jernej, Petrovič Danijel
Laboratory for Histology and Genetics of Atherosclerosis and Microvascular Diseases, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia.
Institute of Histology and Embryology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia.
Biomedicines. 2024 May 16;12(5):1103. doi: 10.3390/biomedicines12051103.
Smad proteins influence the TGFβ signaling pathway, which plays an important role in the progression of atherosclerosis. The aim of our study was to investigate the association between the rs17228212 polymorphism of the SMAD3 gene and advanced carotid atherosclerosis in Slovenian subjects and to investigate the effect of the rs17228212 polymorphism on the expression of SMAD3 in endarterectomy sequesters. In this cross-sectional case-control study, 881 unrelated Caucasians were divided into two groups. The first group included 308 patients with advanced carotid atherosclerosis of the common or internal carotid artery with stenosis greater than 75% that underwent a revascularization procedure (cases). The control group consisted of 573 subjects without hemodynamically significant carotid atherosclerosis. We analyzed the rs17228212 polymorphism of the SMAD3 gene using the StepOne real-time polymerase chain reaction system and TaqMan SNP genotyping assay. The results in the two genetic models showed a statistically significant association, codominant (OR 4.05; CI 1.10-17.75; = 0.037) and dominant (OR 3.60; CI 1.15-15.45; = 0.045). An immunohistochemical analysis of SMAD3 expression was conducted for 26 endarterectomy specimens. The T allele of the rs17228212 SMAD3 gene was shown to be associated with an increased numerical area density of SMAD3-positive cells in carotid plaques.
Smad蛋白影响转化生长因子β（TGFβ）信号通路，该通路在动脉粥样硬化进展中起重要作用。我们研究的目的是调查斯洛文尼亚受试者中SMAD3基因的rs17228212多态性与晚期颈动脉粥样硬化之间的关联，并研究rs17228212多态性对动脉内膜切除术标本中SMAD3表达的影响。在这项横断面病例对照研究中，881名无亲缘关系的高加索人被分为两组。第一组包括308例颈总动脉或颈内动脉晚期颈动脉粥样硬化且狭窄大于75%并接受血运重建手术的患者（病例组）。对照组由573名无血流动力学显著意义的颈动脉粥样硬化受试者组成。我们使用StepOne实时聚合酶链反应系统和TaqMan SNP基因分型检测法分析了SMAD3基因的rs17228212多态性。两种遗传模型的结果显示出统计学上的显著关联，共显性（比值比4.05；可信区间1.10 - 17.75；P = 0.037）和显性（比值比3.60；可信区间1.15 - 15.45；P = 0.045）。对26个动脉内膜切除术标本进行了SMAD3表达的免疫组织化学分析。rs17228212 SMAD3基因的T等位基因与颈动脉斑块中SMAD3阳性细胞的数字面积密度增加有关。
