Department of Experimental Medicine, Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo, Russian Federation.
Immunol Invest. 2022 May;51(4):802-816. doi: 10.1080/08820139.2021.1876085. Epub 2021 Feb 1.
Atherogenesis is mainly determined by endothelial dysfunction, lipid metabolism disorders and inflammation. The atherogenesis-related inflammatory process is a complex interaction between serum blood lipoproteins, inflammatory cells, endothelial and smooth muscle cells and extracellular matrix; the role of chronic inflammation in atherogenesis was proposed.
A pathogenetic role of polymorphism in NF-kB pathway genes in coronary artery disease and associated pathological conditions has been suggested in a case-control retrospective study. 260 coronary artery disease patients permanently living in a large industrial region of Russian Federation (Kemerovo region) were recruited in the study. We examined nine single nucleotide polymorphisms in IL18, IL18R1 and IL18RAP genes by polymerize chain reaction; and serum blood level of IL18 by enzyme-linked immunosorbent assay.
Polymorphic variants rs13015714 (IL18R1) and rs917997 (IL18RAP) are associated with the risk of myocardial infarction and high serum levels of IL18. Minor alleles of rs13015714 and rs917997 sites are associated with high risk of developing multifocal atherosclerosis and arterial hypertension in patients with stable coronary artery disease after myocardial infarction.
Thus, polymorphism in the genes of IL18 receptor is determine the IL18 contents and important in the development of coronary atherosclerosis, associated pathological conditions and the risk of acute coronary events; prospective monitoring of patients with early clinical signs of adverse events is required to confirm the role of IL18, IL18R1, and IL18RAP genes polymorphism in atherogenesis.
动脉粥样硬化主要由内皮功能障碍、脂质代谢紊乱和炎症引起。动脉粥样硬化相关炎症过程是血清脂蛋白、炎症细胞、内皮和平滑肌细胞以及细胞外基质之间的复杂相互作用；提出了慢性炎症在动脉粥样硬化发病机制中的作用。
在一项病例对照回顾性研究中，提出了 NF-kB 通路基因多态性在冠心病及相关病理情况下的发病机制作用。研究共招募了 260 名居住在俄罗斯联邦（克麦罗沃地区）大型工业区的冠心病患者。我们通过聚合酶链反应检测了 IL18、IL18R1 和 IL18RAP 基因中的 9 个单核苷酸多态性，并通过酶联免疫吸附试验检测了血清中 IL18 的水平。
多态性变体 rs13015714（IL18R1）和 rs917997（IL18RAP）与心肌梗死风险和血清 IL18 水平升高相关。rs13015714 和 rs917997 位点的次要等位基因与稳定型冠心病患者心肌梗死后多灶性动脉粥样硬化和动脉高血压的发生风险增加相关。
因此，IL18 受体基因的多态性决定了 IL18 的含量，在冠状动脉粥样硬化的发生发展中起重要作用，与相关的病理状况和急性冠脉事件的风险相关；需要对有早期不良事件临床迹象的患者进行前瞻性监测，以确认 IL18、IL18R1 和 IL18RAP 基因多态性在动脉粥样硬化发病机制中的作用。
