<i>C11orf58</i> (Hero20) Gene Polymorphism: Contribution to Ischemic Stroke Risk and Interactions with Other Heat-Resistant Obscure Chaperones
<b>Background</b>: Recently identified Hero proteins, which possess chaperone-like functions, are promising candidates for research into atherosclerosis-related diseases, including ischemic stroke (IS). <b>Methods</b>: 2204 Russian subjects (917 IS patients and 1287 controls)...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
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| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/12/11/2603 |
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| Summary: | <b>Background</b>: Recently identified Hero proteins, which possess chaperone-like functions, are promising candidates for research into atherosclerosis-related diseases, including ischemic stroke (IS). <b>Methods</b>: 2204 Russian subjects (917 IS patients and 1287 controls) were genotyped for fifteen common SNPs in Hero20 gene <i>C11orf58</i> using probe-based PCR and the MassArray-4 system. <b>Results</b>: Six <i>C11orf58</i> 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(<sub>OG</sub> = 0.02; <sub>SMK</sub> = 0.009; <sub>LFVI</sub> = 0.04)), rs11024032 (EA T; P(<sub>OG</sub> = 0.01; <sub>SMK</sub> = 0.01; <sub>LFVI</sub> = 0.036)), rs11826990 (EA G; P(<sub>OG</sub> = 0.007; <sub>SMK</sub> = 0.004; <sub>LFVI</sub> = 0.03)), rs3203295 (EA C; P(<sub>OG</sub> = 0.016; <sub>SMK</sub> = 0.01; <sub>LFVI</sub> = 0.04)), rs10832676 (EA G; P(<sub>OG</sub> = 0.006; <sub>SMK</sub> = 0.002; <sub>LFVI</sub> = 0.01)), rs4757429 (EA T; P(<sub>OG</sub> = 0.02; <sub>SMK</sub> = 0.04; <sub>LFVI</sub> = 0.04)). The top ten intergenic interactions of Hero genes (two-, three-, and four-locus models) involved exclusively polymorphic loci of <i>C11orf58</i> and <i>C19orf53</i> and were characterized by synergic and additive (independent) effects between SNPs. <b>Conclusions</b>: Thus, <i>C11orf58</i> gene polymorphism represents a major risk factor for IS. Bioinformatic analysis showed the involvement of <i>C11orf58</i> 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, <i>C11orf58</i> interacts most closely with <i>C19orf53</i>. |
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| ISSN: | 2227-9059 |