Shilenok Irina, Kobzeva Ksenia, Soldatov Vladislav, Deykin Alexey, Bushueva Olga
Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia.
Division of Neurology, Kursk Emergency Hospital, 305035 Kursk, Russia.
Biomedicines. 2024 Nov 14;12(11):2603. doi: 10.3390/biomedicines12112603.
: Recently identified Hero proteins, which possess chaperone-like functions, are promising candidates for research into atherosclerosis-related diseases, including ischemic stroke (IS). : 2204 Russian subjects (917 IS patients and 1287 controls) were genotyped for fifteen common SNPs in Hero20 gene using probe-based PCR and the MassArray-4 system. : Six SNPs were significantly associated with an increased risk of IS in the overall group (OG) and significantly modified by smoking (SMK) and low fruit/vegetable intake (LFVI): rs10766342 (effect allele (EA) A; P( = 0.02; = 0.009; = 0.04)), rs11024032 (EA T; P( = 0.01; = 0.01; = 0.036)), rs11826990 (EA G; P( = 0.007; = 0.004; = 0.03)), rs3203295 (EA C; P( = 0.016; = 0.01; = 0.04)), rs10832676 (EA G; P( = 0.006; = 0.002; = 0.01)), rs4757429 (EA T; P( = 0.02; = 0.04; = 0.04)). The top ten intergenic interactions of Hero genes (two-, three-, and four-locus models) involved exclusively polymorphic loci of and and were characterized by synergic and additive (independent) effects between SNPs. : Thus, gene polymorphism represents a major risk factor for IS. Bioinformatic analysis showed the involvement of SNPs in molecular mechanisms of IS mediated by their role in the regulation of redox homeostasis, inflammation, vascular remodeling, apoptosis, vasculogenesis, neurogenesis, lipid metabolism, proteostasis, hypoxia, cell signaling, and stress response. In terms of intergenic interactions, interacts most closely with .
最近发现的具有伴侣样功能的Hero蛋白是研究动脉粥样硬化相关疾病（包括缺血性中风（IS））的有前景的候选对象。对2204名俄罗斯受试者（917名IS患者和1287名对照）使用基于探针的PCR和MassArray-4系统对Hero20基因中的15个常见单核苷酸多态性（SNP）进行基因分型。在总体组（OG）中，6个SNP与IS风险增加显著相关，并受到吸烟（SMK）和低水果/蔬菜摄入量（LFVI）的显著影响：rs10766342（效应等位基因（EA）A；P（总体组=0.02；吸烟=0.009；低水果/蔬菜摄入量=0.04）），rs11024032（EA T；P（总体组=0.01；吸烟=0.01；低水果/蔬菜摄入量=0.036）），rs11826990（EA G；P（总体组=0.007；吸烟=0.004；低水果/蔬菜摄入量=0.03）），rs3203295（EA C；P（总体组=0.016；吸烟=0.01；低水果/蔬菜摄入量=0.04）），rs10832676（EA G；P（总体组=0.006；吸烟=0.002；低水果/蔬菜摄入量=0.01）），rs4757429（EA T；P（总体组=0.02；吸烟=0.04；低水果/蔬菜摄入量=0.04））。Hero基因的前十种基因间相互作用（两位点、三位点和四位点模型）仅涉及Hero20和Hero21的多态性位点，其特征是SNP之间具有协同和加性（独立）效应。因此，Hero20基因多态性是IS的主要危险因素。生物信息学分析表明，Hero20的SNP通过参与氧化还原稳态、炎症、血管重塑、细胞凋亡、血管生成、神经发生、脂质代谢、蛋白质稳态、缺氧、细胞信号传导和应激反应的调节，参与了IS的分子机制。就基因间相互作用而言，Hero20与Hero21的相互作用最为密切。
