Toll样受体4基因多态性（896A/G和1196C/T）作为埃及患者便利样本中COVID-19严重程度的指标
Toll-Like Receptor 4 Polymorphisms (896A/G and 1196C/T) as an Indicator of COVID-19 Severity in a Convenience Sample of Egyptian Patients.
作者信息
Taha Sara I, Shata Aalaa K, Baioumy Shereen A, Fouad Shaimaa H, Anis Sherif G, Mossad Isis M, Moustafa Nouran M, Abdou Dina M, Youssef Mariam K
机构信息
Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Department of Pulmonary Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
出版信息
J Inflamm Res. 2021 Nov 27;14:6293-6303. doi: 10.2147/JIR.S343246. eCollection 2021.
BACKGROUND
The clinical spectrum of COVID-19 is extremely variable. Thus, it is likely that the heterogeneity in the genetic make-up of the host may contribute to disease severity. Toll-like receptor (TLR)-4 plays a vital role in the innate immune response to SARS-CoV-2 infection. The susceptibility of humans to severe COVID-19 concerning TLR-4 single nucleotide polymorphisms (SNPs) has not been well examined.
OBJECTIVE
The goal of this research was to investigate the association between TLR-4 (Asp299Gly and Thr399Ile) SNPs and COVID-19 severity and progression as well as the cytokine storm in Egyptian patients.
METHODS
We genotyped 300 adult COVID-19 Egyptian patients for TLR-4 (Asp299Gly and Thr399Ile) SNPs using PCR-restriction fragment length polymorphism (PCR-RFLP). We also measured interleukin (IL)-6 levels by enzyme-linked immunosorbent assay (ELISA) as an indicator of the cytokine storm.
RESULTS
The minor 299Gly (G) and 399Ile (T) alleles were associated with a significant (P < 0.001) positive risk of severe COVID-19 (OR = 3.14; 95% CI = 2.02-4.88 and OR = 2.75; 95% CI = 1.66-4.57), their frequency in the severe group were 71.8% (84/150) and 70.7% (58/150), respectively. We detected significant differences between TLR-4 (Asp299Gly, Thr399Ile) genotypes with regard to serum levels of IL-6. Levels of IL-6 increased significantly with the presence of the mutant 299Gly (G) and 399Ile (T) alleles to reach the highest levels in the Gly299Gly (GG) and the Ile399Ile (TT) genotypes (170 pg/mL (145-208.25) and 112 pg/mL (24-284.75), respectively).
CONCLUSION
The TLR-4 (Asp299Gly and Thr399Ile) minor alleles 299Gly (G) and 399Ile (T) are associated with COVID-19 severity, mortality, and the cytokine storm.
背景
新型冠状病毒肺炎（COVID-19）的临床谱极为多样。因此，宿主基因组成的异质性可能导致疾病严重程度的差异。Toll样受体（TLR）-4在对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的固有免疫反应中起关键作用。人类对严重COVID-19关于TLR-4单核苷酸多态性（SNP）的易感性尚未得到充分研究。
目的
本研究旨在调查埃及患者中TLR-4（Asp299Gly和Thr399Ile）SNP与COVID-19严重程度、进展以及细胞因子风暴之间的关联。
方法
我们采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术对300例成年埃及COVID-19患者的TLR-4（Asp299Gly和Thr399Ile）SNP进行基因分型。我们还通过酶联免疫吸附测定（ELISA）测量白细胞介素（IL）-6水平，作为细胞因子风暴的指标。
结果
次要等位基因299Gly（G）和399Ile（T）与严重COVID-19的显著（P<0.001）阳性风险相关（比值比[OR]=3.14；95%置信区间[CI]=2.02-4.88，OR=2.75；95%CI=1.66-4.57），它们在重症组中的频率分别为71.8%（84/150）和70.7%（58/150）。我们检测到TLR-4（Asp299Gly、Thr399Ile）基因型在IL-6血清水平方面存在显著差异。随着突变等位基因299Gly（G）和399Ile（T）的出现，IL-6水平显著升高，在Gly299Gly（GG）和Ile399Ile（TT）基因型中达到最高水平（分别为170 pg/mL（145-208.25）和112 pg/mL（24-284.75））。
结论
TLR-4（Asp299Gly和Thr399Ile）次要等位基因299Gly（G）和399Ile（T）与COVID-19的严重程度、死亡率和细胞因子风暴相关。
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