Association of ACE1 I/D polymorphism and susceptibility to COVID-19 in Egyptian children and adolescents
Naglaa F Boraey, Marwa A. Bebars, Ali A. Wahba, Hanan M. Abd El Lateef, Mohamed Atif Attia, Ahmed H. Elsayed, Khalid A. Rashed, Ehab I. Sorour, Mohamed Farouk Ahmed, Ghada A. B. Abd‐Elrehim, Attia A. Soliman, Mohamed M. Shehab, Eman M. Elhindawy, Ahmed A. A. Ibraheem, Hassan Shehata, Yousif M. Yousif, Mustafa Hashem, Amani A. Ahmed, Ahmed A. Emam, Dalia Gameil, Eman M. Abdelhady, Khalil Abdelkhalek, Walaa E. M. A. Morsi, Dalia Selim, Suzan A. Razek, Bassem Ashraf, Ahmed Saleh, Heba H. Eltrawy, Mohamed I. Alanwar, Rania A. Fouad, Walaa E. Omar, Rehab M. Nabil, Mohamed R. Abdelhamed, Mona Yousri Ibrahim, Mai M. Malek, Mona Afify, Mohanned Talal Alharbi, Mohammed K. Nagshabandi, Muyassar K. Tarabulsi, Mohammed Qashqary, Laila M. Almoraie, Hanan Salem, Manal M. Rashad, Sonya Ahmed Ali El-Gaaly, Nahawand A. El- Deeb, Amany AbdAllah, Ahmed R. Fakhreldin, M. A. Hassouba, Yasmine Mahmoud Massoud, Mona Sayed Mohammad Attaya, Mohammed K. Haridi
Abstract
BACKGROUND: Given 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. METHODS: This 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. RESULTS: The 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. CONCLUSIONS: The 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.