Title
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
Creator
Elkilany, Atia Ramadan M., 1969-
Copyright date
2014
Object Links
Select license
Autorstvo 3.0 Srbija (CC BY 3.0)
License description
Dozvoljavate umnožavanje, distribuciju i javno saopštavanje dela, i prerade, ako se navede ime autora na način odredjen od strane autora ili davaoca licence, čak i u komercijalne svrhe. Ovo je najslobodnija od svih licenci. Osnovni opis Licence: http://creativecommons.org/licenses/by/3.0/rs/deed.sr_LATN Sadržaj ugovora u celini: http://creativecommons.org/licenses/by/3.0/rs/legalcode.sr-Latn
Language
English
Cobiss-ID
Theses Type
Doctoral dissertation
description
Datum odbrane: 23.10.2014.
Other responsibilities
mentor
Božić, Biljana, 1975-
član komisije
Magić, Zvonko
član komisije
Šurbatović, Maja
Academic Expertise
Prirodno-matematičke nauke
Academic Title
-
University
Univerzitet u Beogradu
Faculty
Biološki fakultet
Alternative title
Značaj polimorfizama gena za Toll-u slične receptore (TLR) 2, 3 i 4 i gena za receptor za vitamin D za tok i ishod bolesti kod pacijenata sa traumom i/ili sepsom
Publisher
[A. R. M. Elkilany]
Format
100 listova
description
Animal and human physiology - Immunology / Fiziologija životinja i čoveka - Imunologija
Abstract (en)
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...
Abstract (sr)
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...
Authors Key words
tlr genes, vdr genes, polymorphisms, sepsis, trauma, inflammation
Classification
577.2:616.94(043.3)
Type
Tekst
Abstract (en)
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...
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