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Naslov:Pomen izbranih genskih polimorfizmov pri nastanku diabetične ledvične bolezni pri bolnikih s sladkorno boleznijo tipa 2
Avtorji:Šeruga, Maja (Avtor)
Petrovič, Danijel (Mentor) Več o mentorju... Novo okno
Ekart, Robert (Komentor)
Datoteke:.pdf DOK_Seruga_Maja_2018.pdf (1,36 MB)
 
Jezik:Slovenski jezik
Vrsta gradiva:Doktorsko delo/naloga (mb31)
Organizacija:MF - Medicinska fakulteta
Opis:Diabetična nefropatija (DN – izraz, ki ga bolj uporabljamo za biopsijsko dokazano prizadetost ledvic zaradi SB) ali diabetična ledvična bolezen je kronični zaplet pri SB. Proteinurija, povišan krvni tlak in postopen upad ledvične funkcije ob visoki srčno-žilni obolevnosti in umrljivosti so glavne značilnosti razvite diabetične nefropatije pri SB. Okoli 30 do 50% bolnikov razvije klinično očitno DN, vendar ne vemo, kateri bolniki jo bodo razvili in kateri ne. Pravimo, da je DLB večvzročna bolezen in do zdaj so ugotovili, da je v patogenezo okvare ledvice vključenih več genov. Študije o genskem polimorfizmu pri DLB izvajamo z namenom, da bi odkrili gene, ki bi služili kot biomarkerji, in bi na podlagi teh odkritij lahko razvijali terapevtske smernice, s katerimi bi lahko zavrli ali preprečili komplikacije sladkorne bolezni, kot je DLB. Namen naše retrospektivne asociacijske raziskave je bil poiskati povezavo med izbranimi kandidatnimi geni in DLB pri Slovencih s SB2, ki so del kavkaške populacije. V raziskavo smo vključili 651 bolnikov s SB2, ki so imeli bolezen že najmanj 10 let. Za ocenitev ledvične funkcije smo uporabili MDRD enačbo in s-cistatin. Na ta način smo dobili dve skupini bolnikov, in sicer 276 bolnikov z DLB in 375 bolnikov brez DLB, ki so služili kot kontrola. Testirali smo naslednje polimorfizme: polimorfizma rs4340 in rs4341 v genu za angiotenzinsko konvertazo (AK), polimorfizma rs699 in rs4762 v genu za angiotenzinogen (AGT), polimorfizme rs275651, rs931490, rs5182 in rs5186 v genu za receptor tipa 1 za angiotenzin II (AGTR1), polimorfizme rs3087459, rs5370, rs1476046 v genu za endotelin 1 (EDN1), polimorfizem rs3802278 v genu za 5-lipoksigenazo-aktivirajoči proteini (ALOX5AP) in polimorfizem rs12762303 v genu za arahidonat 5-lipoksigenazo (ALOX5). Rezultati niso pokazali statistično pomembne povezave med polimorfizmi rs4340 in rs4341 v genu za angiotenzinsko konvertazo (AK), polimorfizmi rs699 in rs4762 v genu za angiotenzinogen (AGT), polimorfizmi rs275651, rs931490, rs5182 in rs5186 v genu za receptor tipa 1 za angiotenzin II (AGTR1), polimorfizmi rs3087459, rs5370, rs1476046 v genu za endotelin 1 (EDN1) in polimorfizmu rs12762303 v genu za arahidonat 5-lipoksigenazo (ALOX5) in DLB. Nasprotno pa smo ugotovili statistično pomembno povezavo med polimorfizmom rs3802278 v genu za 5-lipoksigenazo-aktivirajoči proteini (ALOX5AP) in DLB. Rezultati logistične regresije so pokazali, da imajo posamezniki z genotipom CC 3,14-krat večjo verjetnost za pojav DLB, v primerjavi s posamezniki z genotipom TT. Torej je genotip CC polimorfizma rs3803278 v genu za ALOX5AP možni dejavnik tveganja za pojav DLB.
Ključne besede:sladkorna bolezen, diabetična ledvična bolezen, genski polimorfizmi
Leto izida:2017
Izvor:Maribor
COBISS_ID: 16604211 Povezava se odpre v novem oknu
Število ogledov:166
Število prenosov:27
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
Področja:MF
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Sekundarni jezik

Jezik:Angleški jezik
Naslov:Role of selected gene polymorphisms in the development of diabetic kidney disease in patients with type 2 diabetes mellitus
Opis:Diabetic nephropathy (DN) is one of the microvascular complications of T2DM. The main characteristics of established diabetic nephropathy are proteinuria, high blood pressure and a gradual decline in renal function, together with increased morbidity and mortality due to cardiovascular complications. DN is a multifactorial disease with environmental and genetic factors involved in its pathogenesis. Multiple genes are involved in developing DN and its distribution depends, amongst other things, on ethnicity. The main purpose of recognising different genes is to find the ones which can identify groups of patients with T2DM who are more likely to develop DN. This can be used as a marker for screening patients with T2DM and focusing on those groups which would benefit from intensive intervention to prevent or slow down complications, such as DN. The main purpose of our retrospective study was to establish a connection between the selected groups of genes in Slovenian patients with T2DM and DN. We selected 651 Slovenian patients with T2DM of at least 10 years duration. We divided patients into two groups: 276 patients had confirmed DN and 375 patients were without clinical signs of DN, the latter acting as the control group. We tested for the following gene polymorphisms: polymorphisms rs4340 and rs4341 in the gene for angiotensin-converting enzyme (ACE), polymorphisms rs699 and 4762 in the gene for angio-tensinogen, polymorphisms rs275651, rs931490, rs5182 and rs5186 in the gene for angiotensin II receptor type 1 (AGTR1), polymorphisms rs3087459, rs5370, rs1476046 in the gene for endothelin 1, polymorphism rs3802278 in the gene for 5-lipoxygenase-activating protein (ALOX5AP), and polymorphism rs12762303 in the gene for arachidonate 5-lipoxygenase (ALOX5). No connection was found between DN and polymorphisms rs4340 and rs4341 in the gene for angiotensin-converting enzyme (ACE), polymorphisms rs699 and rs4762 in the gene for angio-tensinogen, polymorphisms rs275651, rs931490, rs5182 and rs5186 in the gene for angiotensin II receptor type 1 (AGTR1), polymorphisms rs3087459, rs5370, rs1476046 in the gene for endothelin 1 and polymorphism rs12762303 in the gene for arachidonate 5-lipoxygenase (ALOX5). There was, however, a statistically important difference between polymorphism rs3802278 in the gene for 5-lipoxygenase-activating protein (ALOX5AP) in patients with DN (p = 0.004). We concluded that the CC genotype of the ALOXAP5 gene (rs3803278) was associated with a 3.14-fold increased risk of DN in patients with T2DM (95% CI = 1.18-8.35 p = 0.02).
Ključne besede:diabetes mellitus, diabetic nephropathy, gene polymorphisms


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