Analysis of mitochondrial DNA cytochrome-b (CYB) and ATPase-6 gene mutations in COVID-19 patients

J Med Virol. 2022 Jul;94(7):3138-3146. doi: 10.1002/jmv.27704. Epub 2022 Mar 22.

Abstract

Coronavirus disease of 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mutations of mitochondrial DNA (mtDNA) are becoming increasingly common in various diseases. This study aims to investigate mutations in the cytochrome-b (CYB) and adenosine triphosphatase-6 (ATPase-6) genes of mtDNA in COVID-19 patients. The association between mtDNA mutations and clinical outcomes is investigated here. In the present study, mutations of the mtDNA genes CYB and ATPase-6 were investigated in COVID-19 (+) (n = 65) and COVID-19 (-) patients (n = 65). First, we isolated DNA from the blood samples. After the PCR analyses, the mutations were defined using Sanger DNA sequencing. The age, creatinine, ferritin, and CRP levels of the COVID 19 (+) patients were higher than those of the COVID-19 (-) patients (p = 0.0036, p = 0.0383, p = 0.0305, p < 0.0001, respectively). We also found 16 different mutations in the CYB gene and 14 different mutations in the ATPase-6 gene. The incidences of CYB gene mutations A15326G, T15454C, and C15452A were higher in COVID-19 (+) patients than COVID-19 (-) patients; p < 0.0001: OR (95% CI): 4.966 (2.215-10.89), p = 0.0226, and p = 0.0226, respectively. In contrast, the incidences of A8860G and G9055A ATPase-6 gene mutations were higher in COVID-19 (+) patients than COVID-19 (-) patients; p < 0.0001: OR (95%CI): 5.333 (2.359-12.16) and p = 0.0121 respectively. Yet, no significant relationship was found between mtDNA mutations and patients' age and biochemical parameters (p > 0.05). The results showed that the frequency of mtDNA mutations in COVID-19 patients is quite high and it is important to investigate the association of these mutations with other genetic mechanisms in larger patient populations.

Keywords: ATPase-6; COVID-19; CYB; PCR; Sanger sequencing; mtDNA.

MeSH terms

  • Adenosine Triphosphatases* / genetics
  • COVID-19* / genetics
  • Cytochromes b* / genetics
  • DNA, Mitochondrial / genetics
  • Humans
  • Mitochondrial Proton-Translocating ATPases
  • Mutation
  • SARS-CoV-2 / genetics

Substances

  • DNA, Mitochondrial
  • MT-ATP6 protein, human
  • Cytochromes b
  • Adenosine Triphosphatases
  • Mitochondrial Proton-Translocating ATPases