Objectives In March 2020, the World Health Organization declared that an infectious respiratory disease caused by a new severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2, causing coronavirus disease 2019 (COVID-19)] became a pandemic. In our study, we have analyzed a large publicly available dataset, the Genome Aggregation Database (gnomAD), as well as a cohort of 37 Russian patients with COVID-19 to assess the influence of different classes of genetic variants in the angiotensin-converting enzyme-2 ( ACE2 ) gene on the susceptibility to COVID-19 and the severity of disease outcome. Results We demonstrate that the European populations slightly differ in alternative allele frequencies at the 2,754 variant sites in ACE2 identified in the gnomAD database. We find that the Southern European population has a lower frequency of missense variants and slightly higher frequency of regulatory variants. However, we found no statistical support for the significance of these differences. We also show that the Russian population is similar to other European populations when comparing the frequencies of the ACE2 variants. Evaluation of the effect of various classes of ACE2 variants on COVID-19 outcome in a cohort of Russian patients showed that common missense and regulatory variants do not explain the differences in disease severity. At the same time, we find several rare ACE2 variants (including rs146598386, rs73195521, rs755766792, and others) that are likely to affect the outcome of COVID-19. Our results demonstrate that the spectrum of genetic variants in ACE2 may partially explain the differences in severity of the COVID-19 outcome.
【저자키워드】 COVID-19, ACE2, mutations, eQTL, gnomAD, whole-exome sequencing, allele frequency, Russia, 【초록키워드】 coronavirus disease, Coronavirus disease 2019, ACE2, coronavirus, pandemic, susceptibility, severity, disease severity, gnomAD, variant, outcome, variants, Regulatory, Cohort, Respiratory disease, Patient, dataset, genetic variants, Genetic variant, Severity of disease, respiratory, angiotensin-converting enzyme-2, Spectrum, Frequency, angiotensin, Missense, ACE2 variants, Health Organization, Support, World Health Organization, acute respiratory syndrome, frequencies, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, European population, European populations, Genome Aggregation Database, gnomAD database, rs146598386, rs73195521, rs755766792, Russian population, Southern European population, missense variant, Affect, objective, statistical, Result, analyzed, caused, explain, ACE2 variant, alternative allele, patients with COVID-19, 【제목키워드】 ACE2, common, influence,