DNA methylation and gene expression pattern of ACE2 and TMPRSS2 genes in saliva samples of patients with SARS-CoV-2 infection

Abstract

COVID-19 caused by SARS-CoV-2 became a pandemic affecting the health and economy of the world. Although it was known that this virus uses ACE2 protein along with TMPRSS2 to enter the host cell, the methylation pattern and gene expression of ACE2 and TMPRSS2 genes are not explored in saliva samples of patients infected with COVID-19. The study aimed to quantify promoter methylation of ACE2 and TMPRSS2 along with its mRNA expression in saliva samples of COVID-19 patients in order to understand the regulatory mechanism of these genes in SARS-CoV-2 infection. Saliva samples were collected from thirty male patients with SARS-CoV-2 infection and thirty age-matched healthy control male subjects. Q MS PCR and qRT PCR was performed to quantify the promoter DNA methylation and mRNA expression of ACE2 and TMPRSS2 respectively. Our study didnot find any significant difference between methylation and expression of these two genes in cases compared to control subjects. However there was significant positive correlation between DNA methylation of ACE2 and its gene expression. Among cases, the sample collected more than or equal to 7 days after appearance of symptoms showed higher amount of methylation in both ACE2 and TMPRSS2 genes when compared to sample collected before 7 days. In conclusion, we found that ACE2 and TMPRSS2 methylation plays a role in COVID-19.

DNA methylation profiles in pneumonia patients reflect changes in cell types and pneumonia severity

“…Despite being covered by our assay, neither ACE2 nor TMPRSS2 genes, identified in the literature as key players for COVID-19 infection, showed differentially methylated regions in their proximity if comparing cases vs. controls. The same conclusion was reached in a study by Misra et al, despite a different tissue being interrogated [31].…”

Promising use of immune cell‐derived exosomes in the treatment of SARS‐CoV‐2 infections

“…Moreover, a new study quantified promoter DNA methylation of ACE2 and TMPRSS2 genes compared to mRNA expression in saliva samples of COVID‐19 patients. 72 They revealed that DNA methylation of ACE2 has a significant positive relation with mRNA expression of ACE2 in COVID‐19 patients. Interestingly, recent studies highlighted noticeable epigenetic activities in the pathophysiology and severity processes of SARS‐CoV‐2 infections upon the regulation of ACE2 expression.…”

“…As presented in Figure 4, it is possible that enriching MSC‐derived Exos with the EZH2 promoter could efficiently contribute to inducing chromatin remodelling and lowering ACE2 expression, which could help to prevent SARS‐CoV‐2 entry and replication. Moreover, a new study quantified promoter DNA methylation of ACE2 and TMPRSS2 genes compared to mRNA expression in saliva samples of COVID‐19 patients 72 . They revealed that DNA methylation of ACE2 has a significant positive relation with mRNA expression of ACE2 in COVID‐19 patients.…”