Abstract

Epigenetic modifications are known to be effective in the severity and mortality rate of SARS-CoV-2 infection. N6-methyladenosin (m6A) is a posttranscriptional modification that is carried out by m6A methyltransferases (METTL3, METTL14, and WTAP). This modification is effective in the formation of a natural immune response in the relationship between the viral genome and the host cell. In this study, the relationship between clinical severity and METTL3, METTL14, WTAP expression levels in Covid-19 patients was studied for the first time. Also, patients’ D-dimer, ferritin, and C-reactive protein values were compared with these gene expression levels. Total RNA was extracted from blood samples of 100 volunteers and gene expressions were measured using a quantitative real-time polymerase chain reaction. It was determined that METTL3 (p < 0.001) and METTL14 (p = 0.005) genes were statistically significant between case and control. In addition, METTL14 (p = 0.007) and WTAP (p = 0.015) gene expressions were significantly increased in patients with severe disease. METTL14 was statistically significant between the male patients and the control (fold change = 63.87, p = 0.015). Overexpression of the METTL14 gene may have resulted in higher clinical severity in males. Our results demonstrate that host N6-methyladenosine (m6A) methyltransferases may be effective in the development of SARS-CoV-2 infection and prognosis of the disease.

中文翻译：

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Covid-19 患者中 RNA N6-甲基腺苷途径作家基因表达水平和感染的临床严重程度

摘要

已知表观遗传修饰可有效降低 SARS-CoV-2 感染的严重程度和死亡率。N6-甲基腺苷 (m6A) 是一种由 m6A 甲基转移酶（METTL3、METTL14 和 WTAP）进行的转录后修饰。这种修饰对于病毒基因组和宿主细胞之间关系的自然免疫反应的形成是有效的。本研究首次研究了Covid-19患者临床严重程度与METTL3、METTL14、WTAP表达水平之间的关系。此外，还将患者的 D-二聚体、铁蛋白和 C 反应蛋白值与这些基因表达水平进行比较。从 100 名志愿者的血液样本中提取总 RNA，并使用定量实时聚合酶链反应测量基因表达。确定 METTL3 (p < 0.001) 和 METTL14 ( p = 0.005) 基因在病例和对照之间具有统计学显着性。此外，重症患者中METTL14 ( p = 0.007) 和 WTAP ( p = 0.015) 基因表达显着增加。METTL14 在男性患者和对照组之间具有统计学显着性（倍数变化 = 63.87，p = 0.015）。METTL14 基因的过度表达可能导致男性临床严重程度更高。我们的结果表明，宿主 N6-甲基腺苷 (m6A) 甲基转移酶可能对 SARS-CoV-2 感染的发展和疾病的预后有效。