Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran.
Department of Biological Sciences and Technology, Faculty of Materials Engineering, Najafabad Branch, Islamic Azad University, Najafabad, Iran.
Arch Virol. 2023 Mar 23;168(4):119. doi: 10.1007/s00705-023-05729-2.
Coronavirus disease 2019 (COVID-19) is a lethal disease caused by the coronavirus SARS-CoV-2, which can result in a broad clinical spectrum of respiratory symptoms. While many clinical risk factors such as concomitant chronic diseases play roles in the pathophysiology of COVID-19, genetic predisposition factors have not been widely studied. The aim of this study was, therefore, to evaluate the relationship between some singlenucleotide polymorphisms (SNPs) of the human genes TYK2 and ACE2 and the severity of SARS-CoV-2 infection. Genomic DNA was isolated from 200 SARS-CoV-2-infected individuals with severe (n = 100) or mild (n = 100) disease. Owing to the importance of ACE2 and TYK2 genes in regulating the immune response to SARS-CoV-2 infection, TYK2 gene SNPs, i.e. rs2304255, rs2304256, rs12720270, and rs12720354 and ACE2 rs382746 variants, were genotyped in the samples. To confirm the results, the expression of different TYK2 genotypes was investigated using real-time PCR. The presence of the nucleotide T at the locus rs2304255 was shown to be a risk factor linked to disease severity (OR [95% CI] = 3.2485 [2.1554-4.8961]). Similarly, the presence of A at the locus rs12720354 increased the risk of severity (OR [95% CI]) = 3.9721 [2.6075-6.0509]). In contrast, the presence of A at the loci rs2304256 and rs12720270 was observed to reduce the severity risk (OR [95% CI] = 0.2495 [0.1642-0.3793] and 0.1668 [0.1083-0.2569], respectively). Real-time PCR results also demonstrated that the expression level of TYK2 in samples with the TT genotype of rs2304255 and the AA genotype of rs12720354 and in samples with the GG genotype of rs12720207 was significantly lower than in those with other genotypes. The results of this study suggest that TYK2 SNPs might be utilized to identify individuals who are at risk for severe COVID-19, in order to better manage their health care. It is predicted that the presence of some alleles (T in rs2304255, A in rs12720354, and G in rs12720207) of TYK2 can affect COVID-19 severity by reducing TYK2 expression and thereby affecting the regulatory role of TYK2 in the immune response.
新型冠状病毒病 2019（COVID-19）是由冠状病毒 SARS-CoV-2 引起的致命疾病，可导致广泛的呼吸道症状谱。虽然许多临床危险因素，如合并的慢性疾病，在 COVID-19 的病理生理学中起作用，但遗传易感性因素尚未得到广泛研究。因此，本研究的目的是评估人类基因 TYK2 和 ACE2 的一些单核苷酸多态性（SNPs）与 SARS-CoV-2 感染严重程度之间的关系。从 200 名患有严重（n=100）或轻度（n=100）疾病的 SARS-CoV-2 感染个体中分离基因组 DNA。由于 ACE2 和 TYK2 基因在调节对 SARS-CoV-2 感染的免疫反应方面非常重要，因此对 TYK2 基因 SNPs，即 rs2304255、rs2304256、rs12720270 和 rs12720354 以及 ACE2 rs382746 变体进行了基因分型。为了证实结果，使用实时 PCR 研究了不同 TYK2 基因型的表达。结果表明，rs2304255 位点的 T 核苷酸存在是与疾病严重程度相关的危险因素（OR [95%CI] = 3.2485 [2.1554-4.8961]）。同样，rs12720354 位点的 A 存在增加了严重程度的风险（OR [95%CI] = 3.9721 [2.6075-6.0509]）。相比之下，rs2304256 和 rs12720270 位点的 A 存在被观察到降低了严重程度的风险（OR [95%CI] = 0.2495 [0.1642-0.3793] 和 0.1668 [0.1083-0.2569]）。实时 PCR 结果还表明，rs2304255 TT 基因型和 rs12720354 AA 基因型样本以及 rs12720207 GG 基因型样本中 TYK2 的表达水平明显低于其他基因型样本。本研究结果表明，TYK2 SNPs 可用于识别患严重 COVID-19 的高危个体，以便更好地管理他们的医疗保健。据预测，TYK2 的一些等位基因（rs2304255 中的 T、rs12720354 中的 A 和 rs12720207 中的 G）的存在可以通过降低 TYK2 的表达来影响 COVID-19 的严重程度，从而影响 TYK2 在免疫反应中的调节作用。
