o:1722 Uticaj polimorfizma ACE2, IFNL3 i IFNL4 gena na težinu kliničke slike i ishod COVID-19 Association of ACE2, IFNL3 and IFNL4 Gene Polymorphisms with COVID-19 Severity and Outcome : doctoral dissertation sr Uvod: Brojni faktori domaćina, uklučujući i genetičke polimorfizme, mogu uticati nakompleksan mehanizam različitih infektivnih bolesti, poput COVID-19. Genotipizacijomfunkcionalnih polimorfizama relevantnih gena u izloženim populacijama mogu seidentifikovati genetički prediktori teške bolesti i smrtnog ishoda.Cilj: Studija ima za cilj da utvrdi povezanost prisustva polimorfizama ACE2, IFNL3 i IFNL4gena, kao i koncentracija sACE2, IFN-λ3 i IFN-λ4 u serumu, sa težinom bolesti i ishodomCOVID-19.Ispitanici i metode: Ova opservaciona studija obuhvatila je 178 hospitalizovanih pacijenata saSARS-CoV-2 infekcijom. Genotipizacija polimorfizama ACE2, IFNL3 i IFNL4 izvršena jeReal-Time PCR metodom, dok su serumski nivoi sACE2, IFN-λ3 i IFN-λ4 na prijemu određeniELISA metodom.Rezultati: Prisustvo varijantnog alela ACE2 rs2106809 kod žena donosi 12 puta veći rizik odteške forme bolesti, ali i 10 puta manji rizik od kritično teške i smrtnog ishoda. Varijantni aleliIFNL3 (rs8099917 i rs12980275) i IFNL4 (rs12979860 i rs368234815) smanjuju rizik odumerene infekcije najmanje 5 puta. Prisustvo oba varijantna alela bilo kog ispitivanog IFNL4polimorfizma smanjuje rizik od pneumonije kod žena 29 puta i smrtnog ishoda za 93,6%. Šansaza smrtni ishod veća je kod nosilaca varijantnog alela IFNL3 rs8099917. Niži nivoi IFN-λ3 iviši nivoi sACE2 u serumu pacijenata na prijemu ukazuju na povećan rizik od ozbiljnijihkliničkih manifestacija i smrtnog ishoda infekcije SARS-CoV-2.Zaključak: Polimorfizmi ACE2, IFNL3 i IFNL4, kao i serumske koncentracije sACE2 i IFNλ3 na prijemu, povezani su sa težinom i ishodom COVID-19. Genotipizacija ovih gena imerenje serumskih nivoa njihovih produkata u ranim fazama infekcije mogu pomoći u procenirizika od progresije bolesti i smrtnog ishoda. Introduction: Host factors, including genetic polymorphisms, impact the mechanisms ofinfectious diseases such as COVID-19. Genotyping exposed populations for functionalpolymorphisms of relevant genes might predict severe disease and fatal outcome.Aim: This research explores the association of ACE2, IFNL3, and IFNL4 gene polymorphismsand the sACE2, IFN-λ3, and IFN-λ4 serum levels with COVID-19 severity and outcome.Participants and methods: This observational study included 178 hospitalized patients withSARS-CoV-2 infection. Genotyping of ACE2, IFNL3, and IFNL4 polymorphisms wasperformed by the Real-Time PCR method; serum levels of sACE2, IFN-λ3, and IFN-λ4 weredetermined upon admission using the ELISA method.Results: The variant allele of ACE2 rs2106809 in females indicates a 12-fold higher risk ofsevere disease and a 10-fold lower risk of critical severity and fatal outcome. IFNL3 (rs8099917and rs12980275) and IFNL4 (rs12979860 and rs368234815) variant alleles are associated withat least a 5-fold reduced risk of moderate disease. Both variant alleles of any IFNL4polymorphisms are linked to a 29-fold lower risk of pneumonia in females and a 93.6%diminished risk of fatal outcome. The chance of a fatal outcome is higher in carriers of theIFNL3 rs8099917 variant allele. Lower IFN-λ3 and higher sACE2 levels in patients' serum athospital admission indicate an increased risk of severe and fatal SARS-CoV-2 infection.Conclusion: ACE2, IFNL3, and IFNL4 polymorphisms, along with serum concentrations ofsACE2 and IFN-λ3 upon hospital admission, correlate with the COVID-19 severity andoutcome. Genotyping these genes and measuring their product serum levels during the earlystages of infection could assist in assessing the risk of disease progression and fatal outcome. - 91552100 144648457 91552101 8762 2024-07-03T18:13:32.053Z 45 no 46 Sanja, 1992- Matić 93587721 2023 63 komentor Dejan, 1970- Baskić 13558631 2023 63 komentor Nataša, 1975- Đorđević 13560679 2023 63 predsednik komisije Danijela, 1969- Todorović 13821799 2023 63 član komisije Suzana, 1961- Popović 13590631 2023 63 član komisije Zoran, 1963- Todorović 12644711 2023 164 lista 10629251 http://phaidrakg.kg.ac.rs/o:1722 no yes 12 2024-07-03T18:13:32.320Z 70 ACE2; IFNL3; IFNL4; COVID-19; SARS-CoV-2; težina; ishod bolesti; ženskipol ACE2; IFNL3; IFNL4; COVID-19; SARS-CoV-2; severity; outcome; females 575(043.3) 1738 34A05 2023