Title
Association of glutathione transferase A1, M1, P1 and T1 gene polymorphism with oxidative stress byproducts and cardiovascular complications in patiens with end-stage renal disease
Creator
Šuvakov, Sonja R., 1983-
Copyright date
2016
Object Links
Select license
Autorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)
License description
Dozvoljavate samo preuzimanje i distribuciju dela, ako/dok se pravilno naznačava ime autora, bez ikakvih promena dela i bez prava komercijalnog korišćenja dela. Ova licenca je najstroža CC licenca. Osnovni opis Licence: http://creativecommons.org/licenses/by-nc-nd/3.0/rs/deed.sr_LATN. Sadržaj ugovora u celini: http://creativecommons.org/licenses/by-nc-nd/3.0/rs/legalcode.sr-Latn
Language
English
Cobiss-ID
Committee report
Theses Type
Doktorska disertacija
description
Datum odbrane: 28.12.2016.
Other responsibilities
mentor
Simić, Tatjana, 1964-
komentor
Damjanović, Tatjana
član komisije
Dimković, Nada, 1954-
član komisije
Jelić-Ivanović, Zorana, 1951-
član komisije
Stankov, Karmen, 1971-
član komisije
Pekmezović, Tatjana, 1964-
član komisije
Plješa-Ercegovac, Marija, 1976-
Academic Expertise
Medicinske nauke
University
Univerzitet u Beogradu
Faculty
Medicinski fakultet
Alternative title
Povezanost polimorfizama glutation transferaza A1, M1, P1 I T1 sa pokazateljima oksidativnog stresa i kardiovaskularnim komplikacijama kod bolesnika sa terminalnom bubrežnom slabošću
Publisher
[S. R. Šuvakov]
Format
138 listova
description
Medicine - Biochemistry / Medicina - Medicinska biohemija
Abstract (en)
Chronic kidney disease is described as a progressive and irreversible deterioration in kidney
function. When there is less than 10% of nephron function pertained, the patients face endstage
renal disease where renal replacement therapy is needed. Data show that hemodialysis is
the most common method used to treat advanced and permanent kidney failure. Increased
oxidative stress is a hallmark of end-stage renal disease (ESRD). Glutathione transferases
(GST) are involved in the detoxification of xenobiotics and protection of oxidative damage.
The role of polymorphic expression of GSTSs in end-stage renal disease development
enhanced oxidative stress and prognosis of ESRD patients has emerged recently.
The aim of this study was to test if the genetic polymorphism in antioxidant enzymes GSTA1,
GSTM1, GSTP1 and GSTT1 is more frequent in ESRD patients than in control group, and if it
modulates the levels of oxidative stress byproducts and cellular adhesion molecules in these
patients. The association between GSTM1 and GSTT1 deletion polymorphisms as well as
SNPs in GSTA1/rs3957357, GSTP1/rs1695 and rs1138272 genes with overall and causespecific
cardiovascular mortality in patients with end-stage renal disease was also assessed.
Furthermore, the predictive role of oxidative stress byproducts and adhesion molecules level
was also tested.
Individuals with either GSTM1-null or GSTP1*C/*T genotypes were at increased susceptibility
towards ESRD development than individuals with GSTM1-active or GSTP1*C/*C genotypes
(OR = 1.6, p = 0.024 and OR = 3.2, p = 0.001, respectively). This risk was even more
increased when these genotypes were combined with other GST null/low activity genotypes.
Polymorphic expression of GST gene influences the vulnerability to protein and lipid
oxidation, as well as the levels of soluble cellular adhesion molecules in plasma of ESRD
patients. The oxidative stress byproducts were even more increased in terms of combined GST
genotype...
Abstract (sr)
Hronična bubrežna slabost se opisuje kao progresivno i ireverzibilno smanjenje bubrežne
funkcije. Kada se funkcija bubrega smanji na ispod 10% od normalnih vrednosti, nastupa
stanje koje se zove terminalna bubrežna slabost kada je neophodna primena terapije neke od
meoda zamene bubrežne funkcije. Podaci pokazuju da je hemodijaliza najčešće primenjivan
metod. Povećana produkcija slobodnih radikala i stanje oksidativnog stresa glavna su obeležja
terminalne bubrežne slabosti. Glutation transferaze (GST) su enzimi koji su uključeni u
procese eliminacije ksenobiotika i antioksidativne zaštite. Ipak do sada još uvek nije dovoljno
ispitana njihova uloga u podložnosti za razvoj terminalne bubrežne slabosti, oksidativnog
stresa kod ovih bolesnika kao i moguća prediktivna uloga.
Imajući ovo u vidu, cilj ove teze bio je da se ispita veza između polimorfizama gena za GSTA1,
GSTM1, GSTP1 i GSTT1 u podložnosti za razvoj terminalne bubrežne slabosti, kao i da se
utvrdi da li polimorfna ekpresija glutation transferaza utiče na vrednosti produkata
oksidativnog stresa i adhezionih molekula u plazmi bolesnika sa terminalnom bubrežnom
slabošću. Takođe, jedan od ciljeva bio je i da se ispita da li polimorfizam GST gena može da
ima prognostički značaj u smislu opšteg ili kardiovaskularnog preživljavanja kod ovih
bolesnika. Dodatno, ispitan je i prediktivni značaj biohemijskih pokazatelja oksidativnog stresa
i adhezionih molekula.
Osobe koje su imale GSTM1-nulti i GSTP1*C/*T genotip imale su veću podložnost za razvoj
terminalne bubrežne slabosti (OR = 1.6, p = 0.024 and OR = 3.2, p = 0.001, redom), koja je
još više bila izražena kada su se ovi genotipovi kombinovali sa drugim GST nultim ili
genotipovima smanjenih aktivnosti. Takođe, polimorfna ekspresija glutation transferaza kod
bolesnika sa terminalnom bubrežnom slabošću utiče na nivo oksidativnog oštećenja proteina,
lipida i adhezionih molekula...
Authors Key words
end-stage renal disease; glutathione S-transferases polymorphism; hemodialysis;
oxidative stress; adhesion molecules
Authors Key words
terminalna bubrežna slabost, glutation transferaze, polimorfizam, hemodijaliza,
oksidativni stres, ćelijski adhezioni molekuli
Classification
616.61-008:577.1(043.3)
Type
Tekst
Abstract (en)
Chronic kidney disease is described as a progressive and irreversible deterioration in kidney
function. When there is less than 10% of nephron function pertained, the patients face endstage
renal disease where renal replacement therapy is needed. Data show that hemodialysis is
the most common method used to treat advanced and permanent kidney failure. Increased
oxidative stress is a hallmark of end-stage renal disease (ESRD). Glutathione transferases
(GST) are involved in the detoxification of xenobiotics and protection of oxidative damage.
The role of polymorphic expression of GSTSs in end-stage renal disease development
enhanced oxidative stress and prognosis of ESRD patients has emerged recently.
The aim of this study was to test if the genetic polymorphism in antioxidant enzymes GSTA1,
GSTM1, GSTP1 and GSTT1 is more frequent in ESRD patients than in control group, and if it
modulates the levels of oxidative stress byproducts and cellular adhesion molecules in these
patients. The association between GSTM1 and GSTT1 deletion polymorphisms as well as
SNPs in GSTA1/rs3957357, GSTP1/rs1695 and rs1138272 genes with overall and causespecific
cardiovascular mortality in patients with end-stage renal disease was also assessed.
Furthermore, the predictive role of oxidative stress byproducts and adhesion molecules level
was also tested.
Individuals with either GSTM1-null or GSTP1*C/*T genotypes were at increased susceptibility
towards ESRD development than individuals with GSTM1-active or GSTP1*C/*C genotypes
(OR = 1.6, p = 0.024 and OR = 3.2, p = 0.001, respectively). This risk was even more
increased when these genotypes were combined with other GST null/low activity genotypes.
Polymorphic expression of GST gene influences the vulnerability to protein and lipid
oxidation, as well as the levels of soluble cellular adhesion molecules in plasma of ESRD
patients. The oxidative stress byproducts were even more increased in terms of combined GST
genotype...
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