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Association of specific ACE2 and TMPRSS2 variants with circulatory cytokines of COVID-19 Emirati patients.
Elemam, Noha M; Bouzid, Amal; Alsafar, Habiba; Ahmed, Samrein Bm; Hafezi, Shirin; Venkatachalam, Thenmozhi; Eldohaji, Leen; Al Hamidi, Tasneem; Gerges, Peter Habib; Halabi, Nour; Hadj-Kacem, Hassen; Talaat, Iman M; Taneera, Jalal; Sulaiman, Nabil; Maghazachi, Azzam A; Hamid, Qutayba; Hamoudi, Rifat; Saber-Ayad, Maha.
Afiliación
  • Elemam NM; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
  • Bouzid A; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
  • Alsafar H; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
  • Ahmed SB; Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.
  • Hafezi S; Department of Biomedical Engineering, College of Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.
  • Venkatachalam T; Emirates Bio-Research Centre, Ministry of Interior, Abu Dhabi, United Arab Emirates.
  • Eldohaji L; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
  • Al Hamidi T; College of Health, Wellbeing and Life Sciences, Department of Biosciences and Chemistry, Sheffield Hallam University, Sheffield, United Kingdom.
  • Gerges PH; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
  • Halabi N; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
  • Hadj-Kacem H; Department of Physiology and Immunology College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates.
  • Talaat IM; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
  • Taneera J; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
  • Sulaiman N; School of Information Technology and Computer Science (ITCS), Nile University, Giza, Egypt.
  • Maghazachi AA; Al Jalila Genomics Center of Excellence, Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates.
  • Hamid Q; Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates.
  • Hamoudi R; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
  • Saber-Ayad M; Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Front Immunol ; 15: 1348229, 2024.
Article en En | MEDLINE | ID: mdl-38855114
ABSTRACT

Introduction:

The COVID-19 pandemic represented one of the most significant challenges to researchers and healthcare providers. Several factors determine the disease severity, whereas none alone can explain the tremendous variability. The Single nucleotide variants (SNVs) in angiotensin-converting enzyme-2 (ACE2) and transmembrane serine protease type-2 (TMPRSS2) genes affect the virus entry and are considered possible risk factors for COVID-19.

Methods:

We compiled a panel of gene variants from both genes and used in-silico analysis to predict their significance. We performed biological validation to assess their capacity to alter the ACE2 interaction with the virus spike protein. Subsequently, we conducted a retrospective comparative genome analysis on those variants in the Emirati patients with different disease severity (total of 96) along with 69 healthy control subjects.

Results:

Our results showed that the Emirati population lacks the variants that were previously reported as associated with disease severity, whereas a new variant in ACE2 "Chr Xg.15584534" was associated with disease severity specifically among female patients. In-silico analysis revealed that the new variant can determine the ACE2 gene transcription. Several cytokines (GM-CSF and IL-6) and chemokines (MCP-1/CCL2, IL-8/CXCL8, and IP-10/CXCL10) were markedly increased in COVID-19 patients with a significant correlation with disease severity. The newly reported genetic variant of ACE2 showed a positive correlation with CD40L, IL-1ß, IL-2, IL-15, and IL-17A in COVID-19 patients.

Conclusion:

Whereas COVID-19 represents now a past pandemic, our study underscores the importance of genetic factors specific to a population, which can influence both the susceptibility to viral infections and the level of severity; subsequently expected required preparedness in different areas of the world.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Serina Endopeptidasas / Citocinas / Polimorfismo de Nucleótido Simple / Enzima Convertidora de Angiotensina 2 / SARS-CoV-2 / COVID-19 Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Emiratos Árabes Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Serina Endopeptidasas / Citocinas / Polimorfismo de Nucleótido Simple / Enzima Convertidora de Angiotensina 2 / SARS-CoV-2 / COVID-19 Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: Front Immunol Año: 2024 Tipo del documento: Article País de afiliación: Emiratos Árabes Unidos