Genetic association of ACE2 and TMPRSS2 polymorphisms with COVID-19 severity; a single centre study from Egypt.

Autor: Elnagdy MH; Department of Medical Biochemistry and Molecular Biology, Mansoura University Faculty of Medicine, Mansoura, Egypt.; Department of Basic Medical Sciences, Faculty of Medicine, New Mansoura University, Mansoura, Egypt., Magdy A; Department of Medical Biochemistry and Molecular Biology, Mansoura University Faculty of Medicine, Mansoura, Egypt., Eldars W; Department of Basic Medical Sciences, Faculty of Medicine, New Mansoura University, Mansoura, Egypt.; Department of Medical Microbiology and Immunology, Mansoura University Faculty of Medicine, Mansoura, Egypt., Elgamal M; Department of Chest Medicine, Mansoura University Faculty of Medicine, Mansoura, Egypt., El-Nagdy AH; Department of Microbiology, Faculty of Dentistry, Horus University, Damietta El Gadeeda, Egypt., Salem O; Department of Pediatrics, Mansoura University Children's Hospital, Mansoura University Faculty of Medicine, 60 El Gomhouria Street, Mansoura, 35516, Egypt., Elmowafy MM; Intern, Mansoura University Hospitals, Mansoura University, Mansoura, Egypt., Elborsh OA; Intern, Mansoura University Hospitals, Mansoura University, Mansoura, Egypt., Elshafey AW; Intern, Mansoura University Hospitals, Mansoura University, Mansoura, Egypt., Kesba MM; Neurology Resident at Fayoum General Hospital, Faiyum, Egypt., Abdulgalil AE; Mansoura Nephrology and Dialysis Unit, Internal Medicine Department, Mansoura University Faculty of Medicine, Mansoura, Egypt., Sobh A; Department of Pediatrics, Mansoura University Children's Hospital, Mansoura University Faculty of Medicine, 60 El Gomhouria Street, Mansoura, 35516, Egypt. ali.sobh@mans.edu.eg.
Jazyk: angličtina
Zdroj: Virology journal [Virol J] 2024 Jan 23; Vol. 21 (1), pp. 27. Date of Electronic Publication: 2024 Jan 23.
DOI: 10.1186/s12985-024-02298-x
Abstrakt: Background: Since the emergence of the COVID-19 infection in China, it has caused considerable morbidity, mortality, and economic burden. It causes the vast majority of clinical manifestations, ranging from mild or even no symptoms to severe respiratory failure. There are many risk factors for severe COVID-19, such as old age, male gender, and associated comorbidities. A major role for genetic factors may exist. The SARS-CoV-2 virus enters the cell primarily through ACE2 receptors. rs2285666 is one of many polymorphisms found in the ACE2 receptor gene. To enable endosome-independent entry into target cells, the transmembrane protease serine-type 2 (TMPRSS2) is necessary to cleave the virus' spike (S) glycoprotein. TMPRSS2 is characterized by an androgen receptor element. The rs12329760 polymorphism in TMPRSS2 may explain different genetic susceptibilities to COVID-19.
Method: This cross-sectional study was held in Mansoura University Hospitals during the period from June 2020 to April 2022 on patients who had mild and severe COVID-19. Demographic, clinical, and laboratory data were collected, and the TaqMan real-time polymerase chain was used for allelic discrimination in the genotyping of rs2285666 and rs12329760.
Results: This study included 317 Egyptian patients, aged from 0.2 to 87 years. Males were 146, while females were 171. They were divided into mild and severe groups (91 and 226 patients, respectively) based on their clinical symptoms. There was a significant association between COVID-19 severity and male gender, hypertension, diabetes mellitus, and high CRP. The genotype and allele frequency distributions of the ACE2 rs2285666 polymorphism showed no significant association with the severity of COVID-19 in both. In contrast, in TMPRSS2 rs12329760 minor T allele and CT, TT genotypes were significantly associated with a reduced likelihood of developing severe COVID-19.
Conclusion: Our study indicates that the ACE2 rs2285666 polymorphism is not related to the severity of COVID-19, whether genotypes or alleles. In TMPRSS2 rs12329760, the dominant model and T allele showed significantly lower frequencies in severe cases, with a protective effect against severity. The discrepancies with previous results may be due to variations in other ACE2 receptor-related genes, inflammatory mediators, and coagulation indicators. Haplotype blocks and differences in racial makeup must be taken into consideration. Future research should be done to clarify how ethnicity affects these polymorphisms and how other comorbidities combine to have an additive effect.
(© 2024. The Author(s).)
Databáze: MEDLINE
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