RESUMO
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.
Assuntos
COVID-19 , Predisposição Genética para Doença , Peptidil Dipeptidase A , Polimorfismo Genético , SARS-CoV-2 , Humanos , COVID-19/genética , Criança , Egito , Adolescente , Masculino , Peptidil Dipeptidase A/genética , Feminino , Estudos de Casos e Controles , Genótipo , Pré-Escolar , Alelos , Mutação INDEL , Frequência do Gene , Fatores de Risco , Sistema Renina-Angiotensina/genéticaRESUMO
BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore the therapeutic targets of CRC. Long non-coding RNA taurine upregulated gene 1 (LncRNA TUG1) was initially discovered as a transcript upregulated by taurine and is observed to be expressed in numerous human cancers. The Study Aim: This article was to explore the correlation between transforming growth factor-beta (TGF-ß)/tumor protein 53 (P53) signaling mechanisms as regulators for LncRNA TUG1 in Egyptian patients with CRC. SUBJECTS AND METHODS: Immunohistochemical (IHC) staining was achieved to study TGF-ß and P53 expression in CRC specimens vs. normal colonic specimens and quantitative real-time PCR (qRT-PCR) was used to analyze LncRNA TUG1, TGF-ß, and P53 relative gene expression in 96 tissue specimens (neoplastic specimens and the corresponding adjacent non-neoplastic specimens). RESULTS: The expressions of LncRNA TUG1, TGF-ß, and P53 were overexpressed significantly in CRC specimens as opposed to the matched neighboring non-neoplastic specimens (P<0.001), also LncRNA TUG1 was significantly positively correlated to the expression of TGF-ß and P53 (r=0.89, 0.91 respectively, P<0.001). CONCLUSION: These findings reveal that LncRNA TUG1 may be a molecular component in the TGF-ß/P53 signaling pathway, and LncRNA TUG1 could function as a CRC possible oncogene. LncRNA TUG1 may serve as a potential oncogene for CRC. The TGF-ß/P53/LncRNA TUG1 interactions may be employed as potential targets for CRC diagnosis, prognostic evaluation, and cure.