Author: Hassouba, Mohamed ; Eltrawy, Heba H ; Alharbi, Mohanned T ; Abdelhady, Eman M ; Malek, Mai M ; Nabil, Rehab M ; Attia, Mohamed Atif ; Rashad, Manal M ; Selim, Dalia M ; Shehab, Mohamed M M ; Bebars, Marwa A ; Saleh, Ahmed S E ; Shehata, Hassan ; Salem, Hanan F ; Abdelkhalek, Khalil ; Ashraf, Bassem ; Abd-Elrehim, Ghada A B ; Afify, Mona R ; Massoud, Yasmine M ; Abdallah, Amany M ; Boraey, Naglaa F ; Omar, Walaa E ; Ibrahim, Mona Yousri ; Ibraheem, Ahmed A A ; Elsayed, Ahmed H ; Qashqary, Mohammed Esmail ; Wahba, Ali A ; El-Deeb, Nahawand A ; Almoraie, Laila M ; Fakhreldin, Ahmed R ; Ahmed, Amani A ; Razek, Suzan A ; Elhindawy, Eman M ; Abdelhamed, Mohamed R ; Soliman, Attia A ; Nagshabandi, Mohammed K ; Emam, Ahmed A ; Sorour, Ehab I ; Rashed, Khalid A ; Hashem, Mustafa I A ; Morsi, Walaa E M A ; Attaya, Mona S M ; Abd El Lateef, Hanan M ; Gameil, Dalia M ; Ahmed, Mohamed F ; Yousif, Yousif M ; Alanwar, Mohamed I ; El-Gaaly, Sonya A A ; Fouad, Rania A ; Tarabulsi, Muyassar K ; Haridi, Mohammed K

AbstractBackgroundGiven the sparse data on the renin-angiotensin system (RAS) and its biological effector molecules ACE1 and ACE2 in pediatric COVID-19 cases, we investigated whether the ACE1 insertion/deletion (I/D) polymorphism could be a genetic marker for susceptibility to COVID-19 in Egyptian children and adolescents.MethodsThis was a case-control study included four hundred sixty patients diagnosed with COVID-19, and 460 well-matched healthy control children and adolescents. The I/D polymorphism (rs1799752) in the ACE1 gene was genotyped by polymerase chain reaction (PCR), meanwhile the ACE serum concentrations were assessed by ELISA.ResultsThe ACE1 D/D genotype and Deletion allele were significantly more represented in patients with COVID-19 compared to the control group (55% vs. 28%; OR = 2.4; [95% CI: 1.46–3.95]; for the DD genotype; P = 0.002) and (68% vs. 52.5%; OR: 1.93; [95% CI: 1.49–2.5] for the D allele; P = 0.032). The presence of ACE1 D/D genotype was an independent risk factor for severe COVID-19 among studied patients (adjusted OR: 2.6; [95% CI: 1.6–9.7]; P < 0.001.ConclusionsThe ACE1 insertion/deletion polymorphism may confer susceptibility to SARS-CoV-2 infection in Egyptian children and adolescents.Impact

Recent studies suggested a crucial role of renin-angiotensin system and its biological effector molecules ACE1 and ACE2 in the pathogenesis and progression of COVID-19.

To our knowledge, ours is the first study to investigate the association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Caucasian children and adolescents.

The presence of the ACE1 D/D genotype or ACE1 Deletion allele may confer susceptibility to SARS-CoV-2 infection and being associated with higher ACE serum levels; may constitute independent risk factors for severe COVID-19.

The ACE1 I/D genotyping help design further clinical trials reconsidering RAS-pathway antagonists to achieve more efficient targeted therapies.

100 Deals associated with RAS Pathway Targeting(VRise Therapeutics)

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Preclinical	US	Vrise Therapeutics, Inc.	15 May 2024

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