Hashemi Sheikhshabani Somayeh, Ghafouri-Fard Soudeh, Amini-Farsani Zeinab, Modarres Parastoo, Khazaei Feyzabad Sharareh, Amini-Farsani Zahra, Shaygan Nasibeh, Omrani Mir Davood
Student Research Committee, Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Biochem Genet. 2025 Feb;63(1):499-525. doi: 10.1007/s10528-024-10705-9. Epub 2024 Mar 9.
The excessive production of reactive oxygen species and weakening of antioxidant defense system play a pivotal role in the pathogenesis of different diseases. Extensive differences observed among individuals in terms of affliction with cancer, cardiovascular disorders, diabetes, bacterial, and viral infections, as well as response to treatments can be partly due to their genomic variations. In this work, we attempted to predict the effect of SNPs of the key genes of antioxidant defense system on their structure, function, and expression in relation to COVID-19 pathogenesis using in silico tools. In addition, the effect of SNPs on the target site binding efficiency of SNPs was investigated as a factor with potential to change drug response or susceptibility to COVID-19. According to the predicted results, only six missense SNPs with minor allele frequency (MAF) ≥ 0.1 in the coding region of genes GPX7, GPX8, TXNRD2, GLRX5, and GLRX were able to strongly affect their structure and function. Our results predicted that 39 SNPs with MAF ≥ 0.1 led to the generation or destruction of miRNA-binding sites on target antioxidant genes from GPX, PRDX, GLRX, TXN, and SOD families. The results obtained from comparing the expression profiles of mild vs. severe COVID-19 patients using GEO2R demonstrated a significant change in the expression of approximately 250 miRNAs. The binding efficiency of 21 of these miRNAs was changed due to the elimination or generation of target sites in these genes. Altogether, this study reveals the fundamental role of the SNPs of antioxidant defense genes in COVID-19 progression and susceptibility of individuals to this virus. In addition, different responses of COVID-19 patients to antioxidant defense system enhancement drugs may be due to presence of these SNPs in different individuals.
活性氧的过度产生和抗氧化防御系统的减弱在不同疾病的发病机制中起关键作用。个体在患癌症、心血管疾病、糖尿病、细菌和病毒感染以及对治疗的反应方面存在的广泛差异，部分可能归因于其基因组变异。在这项工作中，我们试图使用计算机工具预测抗氧化防御系统关键基因的单核苷酸多态性（SNP）对其结构、功能以及与新冠病毒疾病发病机制相关的表达的影响。此外，还研究了SNP对SNP靶位点结合效率的影响，将其作为一个可能改变药物反应或对新冠病毒易感性的因素。根据预测结果，在基因GPX7、GPX8、TXNRD2、GLRX5和GLRX的编码区中，只有六个次要等位基因频率（MAF）≥0.1的错义SNP能够强烈影响它们的结构和功能。我们的结果预测，39个MAF≥0.1的SNP导致了来自GPX、PRDX、GLRX、TXN和SOD家族的靶抗氧化基因上miRNA结合位点的产生或破坏。使用GEO2R比较轻症与重症新冠患者的表达谱所获得的结果表明，约250个miRNA的表达有显著变化。其中21个miRNA的结合效率因这些基因中靶位点的消除或产生而改变。总之，本研究揭示了抗氧化防御基因的SNP在新冠病毒疾病进展和个体对该病毒易感性中的重要作用。此外，新冠患者对抗氧化防御系统增强药物的不同反应可能是由于不同个体中存在这些SNP。
