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In Silico Prediction of Functional SNPs Interrupting Antioxidant Defense Genes in Relation to COVID-19 Progression
Biochemical Genetics ( IF 2.4 ) Pub Date : 2024-03-09 , DOI: 10.1007/s10528-024-10705-9
Somayeh Hashemi Sheikhshabani , Soudeh Ghafouri-Fard , Zeinab Amini-Farsani , Parastoo Modarres , Sharareh Khazaei Feyzabad , Zahra Amini-Farsani , Nasibeh Shaygan , Mir Davood Omrani

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.



中文翻译:

干扰与 COVID-19 进展相关的抗氧化防御基因的功能性 SNP 的计算机预测

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发挥着关键作用。在癌症、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,个体之间观察到的广泛差异可能部分归因于他们的基因组变异。在这项工作中,我们尝试使用计算机工具预测抗氧化防御系统关键基因的 SNP 对其结构、功能和表达与 COVID-19 发病机制的影响。此外,还研究了 SNP 对 SNP 靶位点结合效率的影响,将其作为可能改变药物反应或对 COVID-19 敏感性的因素。根据预测结果,只有GPX7GPX8TXNRD2GLRX5GLRX基因编码区的6个次要等位基因频率(MAF)≥0.1的错义SNP能够强烈影响其结构和功能。我们的结果预测,MAF ≥ 0.1 的 39 个 SNP 会导致GPXPRDXGLRXTXNSOD家族的靶抗氧化基因上 miRNA 结合位点的产生或破坏。通过比较轻度与 .的表达谱获得的结果。使用 GEO2R 的重症 COVID-19 患者表现出约 250 个 miRNA 表达的显着变化。其中 21 个 miRNA 的结合效率由于这些基因中靶位点的消除或生成而发生变化。总而言之,这项研究揭示了抗氧化防御基因的 SNP 在 COVID-19 进展和个体对该病毒的易感性中的基本作用。此外,COVID-19患者对抗氧化防御系统增强药物的不同反应可能是由于这些SNP在不同个体中的存在所致。

更新日期:2024-03-11
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