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
Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Department of Pulmonary Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
J Inflamm Res. 2021 Nov 27;14:6293-6303. doi: 10.2147/JIR.S343246. eCollection 2021.
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.
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.
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.
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).
The TLR-4 (Asp299Gly and Thr399Ile) minor alleles 299Gly (G) and 399Ile (T) are associated with COVID-19 severity, mortality, and the cytokine storm.
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。
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。
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。
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））。
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。
