Institute of Biochemistry and Molecular Biology, Department of Molecular Biology, Semmelweis University, 1085 Budapest, Hungary.
Department of Anesthesiology and Intensive Therapy, Bács-Kiskun County Teaching Hospital, 6000 Kecskemét, Hungary.
Genes (Basel). 2023 Feb 28;14(3):617. doi: 10.3390/genes14030617.
COVID-19 associated coagulopathy (CAC), characterized by endothelial dysfunction and hypercoagulability, evokes pulmonary immunothrombosis in advanced COVID-19 cases. Elevated von Willebrand factor (vWF) levels and reduced activities of the ADAMTS13 protease are common in CAC. Here, we aimed to determine whether common genetic variants of these proteins might be associated with COVID-19 severity and hemostatic parameters. A set of single nucleotide polymorphisms (SNPs) in the (rs216311, rs216321, rs1063856, rs1800378, rs1800383) and genes (rs2301612, rs28729234, rs34024143) were genotyped in 72 COVID-19 patients. Cross-sectional cohort analysis revealed no association of any polymorphism with disease severity. On the other hand, analysis of variance (ANOVA) uncovered associations with the following clinical parameters: (1) the rs216311 T allele with enhanced INR (international normalized ratio); (2) the rs1800383 C allele with elevated fibrinogen levels; and (3) the rs1063856 C allele with increased red blood cell count, hemoglobin, and creatinine levels. No association could be observed between the phenotypic data and the polymorphisms in the gene. Importantly, in silico protein conformational analysis predicted that these missense variants would display global conformational alterations, which might affect the stability and plasma levels of vWF. Our results imply that missense vWF variants might modulate the thrombotic risk in COVID-19.
COVID-19 相关的凝血功能障碍（CAC），其特征为内皮功能障碍和高凝状态，在重症 COVID-19 患者中引发肺免疫血栓形成。血管性血友病因子（vWF）水平升高和 ADAMTS13 蛋白酶活性降低在 CAC 中很常见。在这里，我们旨在确定这些蛋白的常见遗传变异是否与 COVID-19 严重程度和止血参数相关。在 （rs216311、rs216321、rs1063856、rs1800378、rs1800383）和 基因（rs2301612、rs28729234、rs34024143）中一组单核苷酸多态性（SNP）进行了基因分型，共纳入 72 名 COVID-19 患者。横断面队列分析显示，没有任何多态性与疾病严重程度相关。另一方面，方差分析（ANOVA）揭示了与以下临床参数的关联：（1）rs216311 的 T 等位基因与增强的 INR（国际标准化比值）相关；（2）rs1800383 的 C 等位基因与升高的纤维蛋白原水平相关；（3）rs1063856 的 C 等位基因与增加的红细胞计数、血红蛋白和肌酐水平相关。未观察到表型数据与 基因多态性之间的关联。重要的是，基于结构的蛋白质构象分析预测这些错义变体将显示全局构象改变，这可能会影响 vWF 的稳定性和血浆水平。我们的研究结果表明，错义 vWF 变体可能会调节 COVID-19 中的血栓形成风险。
