TAS2R38 gene methylation is associated with syndrome Coronavirus 2 (SARS-CoV-2) infection and clinical symptoms

Abstract

TAS2R38 is the T2R receptor primarily associated with the innate immune response of the respiratory system. It activates a response mediated by nitric oxide (NO), which has been shown to inhibit the replication of SARS-CoV-2. TAS2R38 polymorphisms (SNPs) that decrease receptor functionality contributing to individual differences in susceptibility to airway infections. DNA methylation (DNAm) may affect gene expression influencing disease development, including COVID-19. We analyzed the effect of SARS-CoV-2 on the methylation pattern of TAS2R38 (at cg25481253, a CpG site located in the coding region) during infection and after the cessation of the exposure to the virus, also considering the disease severity and TAS2R38 SNPs. Our results showed a positive relationship between TAS2R38 DNAm levels and disease severity in the COVID-19 patients and a return to a normal state after the infection. In addition, our results showed an association between DNAm level and the TAS2R38 genotype in participants who recovered from the disease. PAV/PAV genotypes showed lower TAS2R38 DNAm levels than heterozygous and AVI homozygous. In conclusion, our results clearly indicate the involvement of TAS2R38 DNAm alteration in COVID-19 severity and suggest a role of the methylation changes at cg25481253 in the regulation of the TAS2R38 expression.

Keywords: TAS2R38 gene methylation; COVID-19; SNPs of TAS2R38 gene; TAS2R38 receptor.

Fig. 1

Graphic diagram representing the study design.

Fig. 2

TAS2R38 DNAm in COVID-19 positive patients with different severity of the disease and post-COVID-19 participants. n = 51. Distribution of the ∆Ct values and mean values ± SEM for the COVID-19 patients with severe COVID-19 (n = 16), mild-to-moderate COVID-19/asymptomatic (n = 28), and post-COVID-19 (n = 7) are reported. ** indicates a statistically significant difference (P ≤ 0.0031, Dunn’s multiple comparisons test after the Kruskal-Wallis test).

Fig. 3

TAS2R38 DNAm in post-COVID-19 participants, who had previously contracted COVID-19 with different severity of the disease and then recovered. Distribution of the ∆Ct values, and mean values ± SEM, for the participants who had had severe COVID-19 (n = 6), mild-to-moderate COVID-19 (n = 13), and had been asymptomatic (n = 14) are reported. n = 33.

Fig. 4

TAS2R38 DNAm related to TAS2R38 genotype. (A) Distribution of the ∆Ct values, and mean values ± SEM, for the PAV/PAV (n = 8), PAV/AVI (n = 22), and AVI/AVI (n = 12) participants of the first group at the time of the infection (n = 42); (B) Distribution of the ∆Ct values, and mean values ± SEM, for the PAV/PAV (n = 7), PAV/AVI (n = 14), and AVI/AVI (n = 11) recovered participants of the second group (n = 32). * Indicate a significant difference (P ≤ 0.034, Dunn’s multiple comparison test after the Kruskal-Wallis test).