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F2、F7 和 PROS1 凝血基因多态性与 2019 年冠状病毒病疾病严重程度的频率及关联。

Frequency and Association of Polymorphisms in F2, F7, and PROS1 Coagulation Genes with Disease Severity in Coronavirus Disease 2019.

机构信息

Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Department of Infection and Immunity, Research Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.

出版信息

Clin Appl Thromb Hemost. 2024 Jan-Dec;30:10760296241295731. doi: 10.1177/10760296241295731.

Abstract

Abnormal transcriptomic profiles of coagulation genes have been linked to coagulopathies in patients with coronavirus disease 2019 (COVID-19). The objective of the present study was to explore the frequency of genotypes and potential association of polymorphisms in genes encoding coagulation factors with the disease severity in COVID-19 patients.The patients were clinically categorized into four groups of COVID-19 disease severity (asymptomatic, mild, moderate, and severe). Three variants of genes, involving the coagulation genes rs3136516 (F2 gene), rs6042 (F7 gene), and rs6123 (PROS1 gene), were studied. Polymorphisms were genotyped by Sanger DNA sequencing.Most of the subjects had moderate COVID-19 infection (n = 53, 62.4%), followed by mild (n = 16, 18.8%), and severe infections (n = 15, 17.6%). The frequency of the rs3136516 AG genotype was considerably higher in non-ICU patients compared to ICU patients (51.3% vs 34.1%, OR 3.167, 95% CI 1.094-9.170,  = .031). Furthermore, the dominant genetic model (AA + AG vs GG) was significantly associated with a decreased probability of admission to the ICU in COVID-19 patients (OR 0.340, 95% CI 0.127 - 0.905, and  = .028). No other variants of the coagulation genes studied were found to be associated with the severity of COVID-19 disease, admission to the ICU, and mortality ( > .05).The rs3136516 AG genotype could predispose COVID-19 patients to increased disease severity and therefore admission to the ICU, while the dominant genetic model (AA + AG vs GG) of rs3136516 exerts a protective role.

摘要

凝血基因异常转录谱与 2019 年冠状病毒病(COVID-19)患者的凝血疾病有关。本研究旨在探讨编码凝血因子的基因的基因型频率和多态性与 COVID-19 患者疾病严重程度的潜在相关性。

将患者临床分为 COVID-19 疾病严重程度的四组(无症状、轻度、中度和重度)。研究了涉及凝血基因 rs3136516(F2 基因)、rs6042(F7 基因)和 rs6123(PROS1 基因)的三个变体。通过 Sanger DNA 测序对多态性进行基因分型。

大多数患者为中度 COVID-19 感染(n = 53,62.4%),其次是轻度(n = 16,18.8%)和严重感染(n = 15,17.6%)。与 ICU 患者相比,非 ICU 患者的 rs3136516 AG 基因型频率明显更高(51.3%比 34.1%,OR 3.167,95%CI 1.094-9.170, = .031)。此外,显性遗传模型(AA + AG 比 GG)与 COVID-19 患者 ICU 入院概率降低显著相关(OR 0.340,95%CI 0.127 - 0.905, = .028)。未发现研究的凝血基因其他变体与 COVID-19 疾病的严重程度、ICU 入院和死亡率相关( > .05)。

rs3136516 AG 基因型可能使 COVID-19 患者更容易发生疾病加重,从而导致 ICU 入院,而 rs3136516 的显性遗传模型(AA + AG 比 GG)则发挥保护作用。

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