Grbić Emin, Gorkič Nataša, Pleskovič Aleš, Ljuca Farid, Gasparini Mladen, Mrđa Božidar, Cilenšek Ines, Fras Zlatko, Petrovič Daniel
Department of Physiology, Faculty of Medicine, University of Tuzla, Tuzla, Bosnia and Herzegovina.
International Center for Cardiovascular Diseases MC Medicor d.d, Izola, Slovenia.
Gene. 2022 Oct 5;840:146764. doi: 10.1016/j.gene.2022.146764. Epub 2022 Jul 27.
Liver X receptor alpha (LXRA) plays important role in cholesterol and lipid homeostasis and lipid metabolism; moreover, it has been investigated as a candidate gene in a number of conditions, including onset and progression of atherosclerosis. We hypothesized that the LXRA gene rs2279238 polymorphism may be associated with the onset and progression of carotid atherosclerosis in the Slovenian cohort.
783 unrelated Slovenian patients were included in this cross-sectional case-control study: 308 patients in the group of cases with severe internal carotid artery (ICA) stenosis (>75 %) and 475 patients with hemodynamically insignificant ICA stenosis (<50 %) in the control group. Medical records were used to acquire patient laboratory and clinical data. The TaqMan SNP Genotyping assay was used to genotype the rs2279238 polymorphism.
Between the case and control groups, we identified a statistically significant variation in genotype distribution (p = 0.04), but not in allele frequency (p = 0.13) of the LXRA gene polymorphism rs2279238. The results, also show that there is a statistically significant association (p = 0.04) between the two genetic models (codominant and recessive) of the LXRA gene rs2279238 polymorphism and carotid atherosclerosis.
In the Slovenian cohort, we found a significant association between the TT genotype of rs2279238 and advanced carotid artery disease, suggesting that this polymorphism might be a genetic risk factor for ICA atherosclerosis.
肝脏X受体α（LXRA）在胆固醇和脂质稳态以及脂质代谢中发挥重要作用；此外，它已被作为包括动脉粥样硬化的发生和发展在内的多种疾病的候选基因进行研究。我们推测LXRA基因rs2279238多态性可能与斯洛文尼亚队列中颈动脉粥样硬化的发生和发展有关。
本横断面病例对照研究纳入了783名无亲缘关系的斯洛文尼亚患者：308例严重颈内动脉（ICA）狭窄（>75%）患者作为病例组，475例血流动力学无明显意义的ICA狭窄（<50%）患者作为对照组。通过病历获取患者的实验室和临床数据。采用TaqMan SNP基因分型检测法对rs2279238多态性进行基因分型。
病例组和对照组之间，我们发现LXRA基因多态性rs2279238的基因型分布存在统计学显著差异（p = 0.04），但等位基因频率无差异（p = 0.13）。结果还表明，LXRA基因rs2279238多态性的两种遗传模型（共显性和隐性）与颈动脉粥样硬化之间存在统计学显著关联（p = 0.04）。
在斯洛文尼亚队列中，我们发现rs2279238的TT基因型与严重颈动脉疾病之间存在显著关联，提示该多态性可能是ICA粥样硬化的遗传危险因素。
