Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. One open question is whether genetics could influence the severity of symptoms. Considering the limited data on cancer patients, we analyzed public data repositories limited to investigate angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) expressions and genetic variants to identify the basis of individual susceptibility to SARS-CoV-2.Gene expression and variant data were retrieved from Tissue Cancer Genome Atlas, Genotype-Tissue Expression, and gnomAD. Differences in gene expression were tested with Mann-Whitney U-test. Allele frequencies of germline variants were explored in different ethnicities, with a special focus on ACE2 variants located in the binding site to SARS-CoV-2 spike protein.The analysis of ACE2 and TMPRSS2 expressions in healthy tissues showed a higher expression in the age class 20 to 59 years (false discovery rate [FDR] < 0.0001) regardless of gender. ACE2 and TMPRSS2 were more expressed in tumors from males than females (both FDR < 0.0001) and, opposite to the regulation in tissues from healthy individuals, more expressed in elderly patients (FDR = 0.005; FDR < 0.0001, respectively). ACE2 and TMPRSS2 expressions were higher in cancers of elderly patients compared with healthy individuals (FDR < 0.0001). Variants were present at low frequency (range 0% to 3%) and among those with the highest frequency, the variant S19P belongs to the SARS-CoV-2 spike protein binding site and it was exclusively present in Africans with a frequency of 0.2%.The mechanisms of ACE2 and TMPRSS2 regulation could be targeted for preventive and therapeutic purposes in the whole population and especially in cancer patients.Further studies are needed to show a direct correlation of ACE2 and TMPRSS2 expressions in cancer patients and the incidence of COVID-19.
Original language | English |
---|---|
Pages (from-to) | 963689720968749 |
Journal | Cell Transplantation |
Volume | 29 |
DOIs | |
Publication status | Published - Oct 29 2020 |
Keywords
- Adult
- African Continental Ancestry Group/genetics
- Angiotensin-Converting Enzyme 2
- Betacoronavirus/isolation & purification
- Binding Sites
- COVID-19
- Case-Control Studies
- Coronavirus Infections/pathology
- Databases, Genetic
- Female
- Gene Frequency
- Genetic Predisposition to Disease
- Genetic Variation
- Humans
- Incidence
- Male
- Middle Aged
- Neoplasms/epidemiology
- Pandemics
- Peptidyl-Dipeptidase A/genetics
- Pneumonia, Viral/pathology
- SARS-CoV-2
- Serine Endopeptidases/genetics
- Spike Glycoprotein, Coronavirus/chemistry
- Young Adult