https://phaidrabg.bg.ac.rs/o:11047 cobiss:1024817330 thesis:2842 eng 2014 OSNO - Opšta sistematizacija naučnih oblasti, Molekularna imunologija OSNO - Opšta sistematizacija naučnih oblasti, Molekularna imunologija tlr genes, vdr genes, polymorphisms, sepsis, trauma, inflammation 577.2:616.94(043.3) http://creativecommons.org/licenses/by/2.0/at/legalcode info:eu-repo/semantics/bachelorThesis Božić, Biljana, 1975- Magić, Zvonko Šurbatović, Maja The significance of polymorphisms for Toll-like receptors (TLR) 2, 3, and 4 genes, and gene for vitamin D receptor for the course and outcome of the disease in patients with trauma and/or sepsis : doctoral dissertation Elkilany, Atia Ramadan M., 1969- Considering that TLR2, TLR3, TLR4, and VDR play very important role in inflammatory processes, the question arises whether presence of polymorphisms in these genes is associated with susceptibility to sepsis. The aim of this study was to examine the association of TLR2, TLR3, TLR4, and VDR genes polymorphisms with clinical characteristics and outcome of Serbian critically ill patients. A follow-up study was conducted on 121 Caucasian Serbian critically ill patients. Nine polymorphisms in TLRs and VDR genes: TLR2 (rs5743708), TLR3 (rs3775291, rs5743312), TLR4 gene (rs4986790, rs4986791), VDR FokI (rs2228570), VDR TaqI (rs731236), VDR ApaI (rs7975232), and VDR EcoRV (rs4516035) were genotyped by Real Time PCR method. Investigated polymorphisms in TLR2 and TLR4 genes were not associated with clinical characteristics and outcome of critically ill patients. The TLR3 rs3775291 polymorphism was associated with patient’s outcome (p=0.018). Patients with sepsis and TLR3 rs3775291 mutated genotype had four times higher mortality rate compared to the wild type and heterozygous carriers. Multivariate regression analysis showed that age, sex and TLR3 rs3775291 polymorphism are independent variables of outcome of critically ill patients. For the first time, our preliminary findings indicate role of TLR3 with MyD88 independent signaling and its polymorphism (TLR3 rs3775291) in sepsis and survival in Serbian critically ill patients. Further, in this study statistically significant difference in the frequency of VDR FokI (rs2228570) between the critically ill patients and healthy subjects is shown. However, in patients with trauma, who did not develop sepsis, did not detected VDR FokI mutated genotype. Multivariate regression analysis which was used to asses the independent variables that may affect mortality of critically ill patients, showed that age, and VDR FokI rs2228570 polymorphism are statistically significant variables... Imajući u vidu da TLR2, TLR3, TLR4 i VDR igraju veoma važnu ulogu u procesu inflamacije, posatvlja se pitanje da li je prisustvo polimorfizama ovih gena pitanje u vezi sa mogućnođću za razvoj sepse. Cilj ovog istraživanja je ispitivanje asocijacije polimorfizama TLR2, TLR3, TLR4 i VDR gena sa kliničkim karakteristikama i ishodom vitalno ugroženih pacijenata sa intenzivnom negom u Srbiji. Studija je uključila 121 vitalno ugroženog pacijenata sa intenzivnom negom bele rase u Srbiji. Izvršena uje genotipizacija devet polimorfizama TLR i VDR gena: TLR2 (rs5743708), TLR3 (rs3775291, rs5743312), TLR4 gene (rs4986790, rs4986791), VDR FokI (rs2228570), VDR TaqI (rs731236), VDR ApaI (rs7975232), i VDR EcoRV (rs4516035) primenom Real Time PCR metode. Ispitiani polimorfizmi u TLR2 i TLR4 genima nisu povezani sa kliničkim karakteristikama i ishodom vitalno ugroženih pacijenata sa intenzivnom negom. TLR3 rs3775291 polimorfzam je povezan sa ishodom vitalno ugroženih pacijenata sa intenzivnom negom (p=0.018). Pacijenti sa sepsom i TLR3 rs3775291 mutiranim genotipom imaju četiri puta veći stepen mortaliteta u poređenju sa nosiocima wild type genotipa i heterozigotima. Multivarijantna regresiona analiza je pokazala da su godine, pol i TLR3 rs3775291 polimorfizam nezavisne varijable ishoda vitalno ugroženih pacijenata sa intenzivnom negom. Po prvi put, nađi preliminarni nalazi ukazuju na ulogu TLR3 sa MyD88 nezavisnom signalizacijom i njegovog polimorfizma (TLR3 rs3775291) u sepsi i preživljavanju vitalno ugroženih pacijenata sa intenzivnom negom u Srbiji. Dalje, u ovoj studiji je pokazana statistički zmačajna razlika u zastupljenosti VDR FokI (rs2228570) polimorfizma izmežu vitalno ugroženih pacijenata sa intenzivnom negom i zdravih osoba. Međutim, kod pacijenata sa traumom koji nisu razviji sepsu nije detektovano prisustvo VDR FokI mutatiranog genotipa. Multivarijantna regresiona analiza koja se koristi za procenu nezavisnih varijabli koje mogu da utiču na mortalitet vitalno ugroženih pacijenata sa intenzivnom negom pokazala je da su godine i VDR FokI rs2228570 polimorfizam statistički značajne varijable... Animal and human physiology - Immunology / Fiziologija životinja i čoveka - Imunologija Datum odbrane: 23.10.2014 100 listova 1814196 bytes