Abstract Severe acute respiratory syndrome coronavirus 2 infection produces a wide spectrum of manifestations, ranging from no symptom to viral pneumonia. This study aimed to determine the genetic variations in cytokines and their receptors in relation to COVID‐19 pathogenesis using bioinformatic tools. Single nucleotide polymorphisms (SNPs) of genes encoding the cytokines and cytokine receptors elevated in patients with COVID‐19 were determined from the National Biotechnology Information Center website (using the dbSNP database). Missense variants were found in 3 cytokine genes and 10 cytokine receptor genes. Computational analyses were conducted to detect the effects of these missense SNPs via cloud‐based software tools. Also, the miRSNP database was used to explore whether SNPs in the 3′‐UTR altered the miRNA binding efficiency for genes of cytokines and their receptors. Our in silico studies revealed that one SNP in the vascular endothelial growth factor receptor 2 (VEGFR2) gene was predicted as deleterious using sorting intolerant from tolerant. Also, the stability of VEGFR2 decreased in the I‐Mutant2.0 (biotool for predicting stability changes upon mutation from the protein sequence or structure) prediction. It was suggested that the decrease in VEGFR2 function (due to the rs1870377 polymorphism) may be correlated with the progression of COVID‐19 or contribute to the pathogenesis. Moreover, 27 SNPs were determined to affect miRNA binding for the genes of cytokine receptors. CXCR2 rs1126579, TNFRSF1B rs1061624 and IL10RB rs8178562 SNPs were predicted to break the miRNA‐mRNA binding sites for miR‐516a‐3, miR‐720 and miR‐328, respectively. These miRNAs play an important role in immune regulation and lung damage repair. Further studies are needed to evaluate the importance of these miRNAs and the SNPs.

中文翻译：

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一种研究与 COVID-19 进展相关的细胞因子基因及其受体变体的生物信息学方法

摘要 严重急性呼吸综合征冠状病毒 2 感染会产生广泛的表现，从无症状到病毒性肺炎。本研究旨在使用生物信息学工具确定与 COVID-19 发病机制相关的细胞因子及其受体的遗传变异。从国家生物技术信息中心网站（使用 dbSNP 数据库）确定了编码 COVID-19 患者升高的细胞因子和细胞因子受体的基因的单核苷酸多态性 (SNP)。在 3 个细胞因子基因和 10 个细胞因子受体基因中发现了错义变异。进行计算分析以通过基于云的软件工具检测这些错义 SNP 的影响。还，miRNSNP 数据库用于探索 3'-UTR 中的 SNP 是否改变了细胞因子及其受体基因的 miRNA 结合效率。我们的计算机研究表明，血管内皮生长因子受体 2 (VEGFR2) 基因中的一个 SNP 被预测为有害，使用从耐受中分选不耐受。此外，在 I-Mutant2.0（用于预测蛋白质序列或结构突变后稳定性变化的生物工具）预测中，VEGFR2 的稳定性降低。有人提出，VEGFR2 功能的降低（由于 rs1870377 多态性）可能与 COVID-19 的进展相关或有助于发病机制。此外，确定了 27 个 SNP 影响细胞因子受体基因的 miRNA 结合。CXCR2 rs1126579, 预测 TNFRSF1B rs1061624 和 IL10RB rs8178562 SNP 分别破坏 miR-516a-3、miR-720 和 miR-328 的 miRNA-mRNA 结合位点。这些miRNA在免疫调节和肺损伤修复中发挥重要作用。需要进一步的研究来评估这些 miRNA 和 SNP 的重要性。