Analysis of the Spectrum of ACE2 Variation Suggests a Possible Influence of Rare and Common Variants on Susceptibility to COVID-19 and Severity of Outcome.

Autor:	Shikov AE; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia.; Saint Petersburg State University, Saint Petersburg, Russia., Barbitoff YA; Saint Petersburg State University, Saint Petersburg, Russia.; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia.; Bioinformatics Institute, Saint Petersburg, Russia., Glotov AS; Saint Petersburg State University, Saint Petersburg, Russia.; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia., Danilova MM; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia., Tonyan ZN; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia., Nasykhova YA; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia., Mikhailova AA; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia., Bespalova ON; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia., Kalinin RS; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Mirzorustamova AM; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Kogan IY; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia., Baranov VS; Saint Petersburg State University, Saint Petersburg, Russia.; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia., Chernov AN; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Pavlovich DM; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Azarenko SV; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Fedyakov MA; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Tsay VV; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Eismont YA; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Romanova OV; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Hobotnikov DN; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Vologzhanin DA; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Mosenko SV; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Ponomareva TA; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Talts YA; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Anisenkova AU; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Lisovets DG; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Sarana AM; Saint Petersburg State University, Saint Petersburg, Russia., Urazov SP; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia., Scherbak SG; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia.; Saint Petersburg State University, Saint Petersburg, Russia., Glotov OS; Genetics Laboratory, City Hospital No. 40, Saint Petersburg, Russia.; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2020 Sep 29; Vol. 11, pp. 551220. Date of Electronic Publication: 2020 Sep 29 (Print Publication: 2020).
DOI:	10.3389/fgene.2020.551220
Abstrakt:	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. (Copyright © 2020 Shikov, Barbitoff, Glotov, Danilova, Tonyan, Nasykhova, Mikhailova, Bespalova, Kalinin, Mirzorustamova, Kogan, Baranov, Chernov, Pavlovich, Azarenko, Fedyakov, Tsay, Eismont, Romanova, Hobotnikov, Vologzhanin, Mosenko, Ponomareva, Talts, Anisenkova, Lisovets, Sarana, Urazov, Scherbak and Glotov.)
Databáze:	MEDLINE
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