The association of ACE1, ACE2, TMPRSS2, IFITM3 and VDR polymorphisms with COVID-19 severity

A systematic review and meta-analysis

Authors

  • Zorana Dobrijević Department for Metabolism, Institute for the Application of Nuclear Energy (INEP), University of Belgrade, Belgrade, Serbia. Tel: +381 11 2618 666, E-mail: zorana.dobrijevic@inep.co.rs https://orcid.org/0000-0002-4652-7719
  • Dragana Robajac University of Belgrade – Institute for the Application of Nuclear Energy (INEP), Belgrade, Serbia https://orcid.org/0000-0002-6423-4645
  • Nikola Gligorijević University of Belgrade – Institute for the Application of Nuclear Energy (INEP), Belgrade, Serbia https://orcid.org/0000-0002-8691-2486
  • Miloš Šunderić University of Belgrade – Institute for the Application of Nuclear Energy (INEP), Belgrade, Serbia https://orcid.org/0000-0002-0940-9481
  • Ana Penezić University of Belgrade – Institute for the Application of Nuclear Energy (INEP), Belgrade, Serbia https://orcid.org/0000-0002-2539-4507
  • Goran Miljuš University of Belgrade – Institute for the Application of Nuclear Energy (INEP), Belgrade, Serbia https://orcid.org/0000-0001-6417-8711
  • Olgica Nedić University of Belgrade – Institute for the Application of Nuclear Energy (INEP), Belgrade, Serbia https://orcid.org/0000-0003-2042-0056

DOI:

https://doi.org/10.17179/excli2022-4976

Keywords:

COVID-19, ACE1, ACE2, TMPRSS2, IFITM3, VDR

Abstract

Genes involved in the regulation of viral recognition and its entry into a host cell have been identified as candidates for genetic association studies on COVID-19 severity. Published findings on the effects of polymorphisms within ACE1, ACE2, TMPRSS2, IFITM3 and VDR genes remained inconclusive, so we conducted a systematic review and meta-analysis in order to elucidate their potential involvement in the genetic basis underlying the severity of COVID-19 and/or an outcome of SARS-CoV-2 infection. Identification of potentially eligible studies was based on PubMed, Scopus and Web of Science database search. Relevant studies (n=29) with a total number of 8247 SARS-CoV-2-positive participants were included in qualitative synthesis, while results of 21 studies involving 5939 were pooled in meta-analysis. Minor allele I of rs1799752 located within ACE1 was identified as a protective variant against severe COVID-19, while its effect on mortality rate was opposite. Similarly, minor allele A of ACE2 polymorphism, rs2285666, was found to associate with a decreased risk of severe COVID-19 (P = 0.003, OR = 0.512, 95 % CI = 0.331-0.793). Statistical significance was also seen for the association between COVID-19 severity and rs12329760 located within TMPRSS2. Our results did not support the supposed association of rs12252 in IFITM3 and polymorphisms within VDR with disease severity. We conclude that genetic variants within ACE1, ACE2 and TMPRSS2 may be potential biomarkers of COVID-19 severity, which needs to be further confirmed in a larger set of studies.

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Published

2022-06-20

How to Cite

Dobrijević, Z., Robajac, D., Gligorijević, N., Šunderić, M., Penezić, A., Miljuš, G., & Nedić, O. (2022). The association of ACE1, ACE2, TMPRSS2, IFITM3 and VDR polymorphisms with COVID-19 severity: A systematic review and meta-analysis. EXCLI Journal, 21, 818–839. https://doi.org/10.17179/excli2022-4976

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Review articles

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