Karpenko Andrey R, Kobzeva Ksenia A, Orlov Yuriy L, Bushueva Olga Yu
Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia.
Department of Anesthesia and Critical Care, Institute of Continuing Education, Kursk State Medical University, 305004 Kursk, Russia.
Int J Mol Sci. 2025 Sep 15;26(18):8967. doi: 10.3390/ijms26188967.
In viral infections human heat shock proteins (HSPs) play a dual role by either protecting host cells or acting on viruses' needs. The roles of HSPs have been extensively studied in various human pathologies, but their involvement in the progression of COVID-19 remains unexplored. It makes HSPs genetic variants particularly interesting in the context of severe COVID-19 risk. In this study, 1228 subjects (199 hospitalized COVID-19 patients and 962 controls) were genotyped for 20 SNPs in genes encoding and their regulators. SNP rs7189628 (effect allele [EA] T) increased the risk of severe COVID-19 in the entire group ( = 0.002), males ( = 0.00008), and smokers ( = 0.0003). SNP rs910652 (EA C) decreased the risk of severe COVID-19 in the entire group ( = 0.01), females ( = 0.04), and patients with normal physical activity levels ( = 0.01). SNP rs1136141 (EA A) increased the risk of severe COVID-19 in patients with low fruit/vegetable intake ( = 0.004). Moreover, we observed significant changes in ground-glass opacity and alterations in blood coagulation and inflammation parameters, influenced by the SNPs of , , , , , and . The molecular mechanisms underlying these associations are discussed. Together, our study provides preliminary evidence that SNPs of HSPs can significantly modulate the risk of severe COVID-19.
在病毒感染中，人类热休克蛋白（HSPs）发挥着双重作用，既保护宿主细胞，又满足病毒的需求。HSPs的作用已在各种人类疾病中得到广泛研究，但其在COVID-19进展中的作用仍未得到探索。在严重COVID-19风险的背景下，HSPs基因变异尤其令人关注。在本研究中，对1228名受试者（199名住院COVID-19患者和962名对照）进行了编码HSPs及其调节因子的基因中20个单核苷酸多态性（SNP）的基因分型。SNP rs7189628（效应等位基因[EA]为T）增加了整个研究组（P = 0.002）、男性（P = 0.00008）和吸烟者（P = 0.0003）发生严重COVID-19的风险。SNP rs910652（EA为C）降低了整个研究组（P = 0.01）、女性（P = 0.04）和身体活动水平正常的患者（P = 0.01）发生严重COVID-19的风险。SNP rs1136141（EA为A）增加了水果/蔬菜摄入量低的患者发生严重COVID-19的风险（P = 0.004）。此外，我们观察到，受HSPB1、HSPB5、HSP90AA1、HSP90AB1、HSPA1A和HSPA1B的SNP影响，磨玻璃影以及凝血和炎症参数发生了显著变化。讨论了这些关联背后的分子机制。总之,我们的研究提供了初步证据，表明HSPs的SNP可显著调节严重COVID-19的风险。
