TLR3和TLR9基因多态性在评估COVID-19严重程度中的预后意义

L. Ashchina, N. I. Baranova, A. Bolgova, O. A. Levashova, O. N. Lesina
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Frequency analysis of TLR9 (rs352140) in COVID-19 patients showed significantly higher values of the ST genotype and lower values of the CC genotype compared to healthy individuals. Comparative analysis between groups of hospitalized patients depending on severity revealed higher frequency of ST genotype and lower frequency of TT genotype of TLR3 (rs3775291) and TLR9 (rs352140) genes in patients with severe and extremely severe condition.Conclusion: reliable differences in the frequency of occurrence of genotypes of TLR3 (rs3775291) and TLR9 (rs352140) genes in patients with the manifest form of COVID-19 compared to healthy people were revealed. The analysis of nucleotide sequence variants of the studied genes in hospitalized patients depending on the degree of severity also showed significant differences in the frequency of genotypes. 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摘要

材料与方法:对164名COVID-19患者的TLR3(rs3775291)和TLR9(rs352140)基因多态性进行遗传分析:第一组为轻度,第二组为中度,第三组为重度和极重度。对照组由 40 名健康供体组成。所得结果使用 STATISTICA 12.0 程序(Stat Soft,美国)进行统计处理。为了根据定性特征评估组间差异,使用了带有 Yates 校正的 χ2 标准,如果违反其条件,则使用 χ2 标准。如果违反其适用条件,则采用费雪双侧标准(RF)。组间差异在 р ˂ 0.05 时具有统计学意义。结果显示:与对照组相比,COVID-19表现型患者的TLR3基因rs3775291等位基因的ST基因型频率明显较高,TT基因型频率明显较低。COVID-19患者TLR9(rs352140)的频率分析显示,与健康人相比,ST基因型的值明显较高,而CC基因型的值较低。结论:与健康人相比,显性 COVID-19 患者的 TLR3(rs3775291)和 TLR9(rs352140)基因型出现频率存在可靠差异。根据病情严重程度对住院病人所研究基因的核苷酸序列变异进行的分析也显示出基因型频率的显著差异。因此,在重度和极重度 COVID-19 患者中,与轻度和中度 COVID-19 患者相比,TLR3(rs3775291)和 TLR9(rs352140)基因的 ST 和 TT 基因型出现频率存在显著差异,这可能对评估疾病的严重程度有进一步的预后价值。
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Prognostic significance of TLR3 and TLR9 gene polymorphism in assessing the severity of COVID-19
Objective: to study polymorphic variants of TLR3 (rs3775291) and TLR9 (rs352140) genes in patients with COVID-19 depending on the severity of the disease and their significance for determining the risk of severe course of COVID-19.Materials and Methods: genetic analysis of polymorphism of TLR3 (rs3775291) and TLR9 genes (rs352140) was performed in 164 patients with COVID-19, who were divided by degree of severity into three groups: Group 1 with mild, Group 2 with moderate and Group 3 with severe and extremely severe degrees of severity. The control group consisted of 40 healthy donors. Statistical processing of the obtained results was carried out using STATISTICA 12.0 programs (Stat Soft, USA). To assess the difference of groups by qualitative characteristics, the χ2 criterion with Yates correction was used, and in case of violation of its conditions, the χ2 criterion was applied. Yates correction, and if the conditions of its applicability were violated, the two-sided Fisher’s two-sided criterion (RF). The difference between the groups was considered statistically significant at р<0,05. The strength of associations was evaluated in the values of the odds ratio index odds ratio (OR) and 95% confidence interval.> ˂ 0,05. The strength of associations was evaluated in the values of the odds ratio index odds ratio (OR) and 95% confidence interval.Results: the frequency of the ST genotype was significantly higher and the frequency of the TT genotype of the rs3775291 allele of the TLR3 gene was significantly lower in patients with the manifest form of COVID-19 compared with the control group. Frequency analysis of TLR9 (rs352140) in COVID-19 patients showed significantly higher values of the ST genotype and lower values of the CC genotype compared to healthy individuals. Comparative analysis between groups of hospitalized patients depending on severity revealed higher frequency of ST genotype and lower frequency of TT genotype of TLR3 (rs3775291) and TLR9 (rs352140) genes in patients with severe and extremely severe condition.Conclusion: reliable differences in the frequency of occurrence of genotypes of TLR3 (rs3775291) and TLR9 (rs352140) genes in patients with the manifest form of COVID-19 compared to healthy people were revealed. The analysis of nucleotide sequence variants of the studied genes in hospitalized patients depending on the degree of severity also showed significant differences in the frequency of genotypes. Thus, in patients with severe and extremely severe COVID-19, a significant difference in the frequency of occurrence of ST and TT genotypes of TLR3 (rs3775291) and TLR9 (rs352140) genes was revealed compared to patients with mild and moderate COVID-19, which may further have prognostic value in assessing the severity of the disease.
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