magistrski študij laboratorijske biomedicine
Maja Murkovič (Avtor), Mojca Božič (Mentor)

Povzetek

Za periferno arterijsko bolezen (PAB) je značilna nezadostna oskrba perifernih tkiv z oksigenirano krvjo, ki jo v večini primerov povzroča ateroskleroza. Običajno so prizadete arterije spodnjih okončin. Kot posledica nezadostne prekrvavitve se pri bolnikih pojavi krčevita bolečina v mišicah nog. Ker je PAB v večini primerov posledica generalizirane ateroskleroze imajo ti bolniki večje tveganje za druge srčno-žilne dogodke. Za diagnosticiranje bolezni se uporablja meritev gleženjskega indeksa (GI). V primeru napredovale PAB (kritična ishemija uda ali moteča krčevita bolečina) je potrebno opraviti revaskularizacijske posege. Za zdravljenje krajših zožitev se uporablja perkutana transluminalna angioplastika (PTA), ki je kljub dobri primarni uspešnosti omejena z razvojem restenoze. Na razvoj PAB vplivajo dejavniki tveganja in genetska predispozicija. Dokazano je, da se GI v veliki meri deduje, vendar še ni znano za katere genske spremembe gre. Namen naloge je bil ugotoviti povezavo med polimorfizmi rs12803, rs146608 in rs13428968 v genu NR4A2, rs668 in rs12953 v genu PECAM1, rs10499563 v genu IL6 ter rs10861032 na kromosomu 12 in PAB, srčno-žilnimi dogodki ter restenozo po PTA. V ta namen smo zastavili dve raziskavi. V raziskavo A smo vključili 662 bolnikov s PAB in 615 bolnikov brez PAB, v raziskavo B pa 182 bolnikov z opravljeno PTA. Pri vseh bolnikih smo z reakcijo PCR v realnem času pomnožili odseke DNA, kjer se nahajajo polimorfizmi ter z alelno diskriminacijo določili genotipe. V nalogi smo ugotovili, da preučevani polimorfizmi niso pogostejši pri bolnikih s PAB v primerjavi z vrstniki brez bolezni. Pri razdelitvi bolnikov na tiste, ki so utrpeli srčno-žilni dogodek in tiste brez dogodka pa smo odkrili, da so s pogostostjo srčno-žilnih dogodkov šibko povezani polimorfizmi rs668 v genu PECAM1, rs10499563 v genu IL6 in rs10861032 na kromosomu 12 ter haplotip 4 v PECAM1. Pri rs668 je bil genotip GG povezan z 1,5-krat večjim tveganjem za večji dogodek, pri rs10499563 je bil genotip TT povezan z 1,6-krat večjim tveganjem za manjši dogodek, pri rs10861032 je bil genotip CC povezan z 2,4-krat večjim tveganjem za kakršnikoli oz. z 2,6-krat večjim tveganjem za manjši dogodek, pri haplotipih PECAM1 pa je bil haplotip 4 povezan z 2,9-krat večjim tveganjem za kakršnikoli oz. z 3,9-krat večjim tveganjem za manjši dogodek. Za polimorfizme rs12803, rs146608 in rs13428968 v genu NR4A2 nismo ugotovili povezave s pogostostjo srčno-žilnih dogodkov. Z restenozo po PTA sta bila šibko povezana polimorfizma rs668 v genu PECAM1 in rs10499563 v genu IL6. Pri polimorfizmu rs668 je bil genotip GG povezan z 1,9-krat manjšim tveganjem, pri polimorfizmu rs10499563 pa je bil genotip TT povezan z 2,3-krat večjim tveganjem. Za polimorfizme rs12803, rs146608 in rs13428968 v genu NR4A2, rs12953 v genu PECAM1 in rs10861032 na kromosomu 12 nismo dokazali povezave z restenozo po PTA. Odsotnost povezave nekaterih polimorfizmov kandidatnih genov s PAB, srčno-žilnimi dogodki in restenozo bi lahko bila posledica značilnosti preiskovancev, njihovega števila ali pa dejanske odsotnosti povezave. Na omenjene procese vplivajo številni dejavniki tveganja. Za ugotovitev povezave polimorfizmov kot neodvisnih dejavnikov tveganja bi bilo potrebno pri statistični analizi podatkov upoštevati tudi te dejavnike. Glede na to, da smo našli le šibke povezave, bi bilo potrebno ugotovitve potrditi na večji skupini preiskovancev. Smiselno bi bilo preučiti tudi povezavo medsebojne interakcije polimorfizmov z razvojem PAB, srčno-žilnih dogodkov in restenoze.

Ključne besede

srčnožilni dogodki;restenoza;polimorfizmi;genetski kazalniki;določitev genotipov;raziskave;

Podatki

Jezik: Slovenski jezik
Leto izida:
Izvor: Ljubljana
Tipologija: 2.09 - Magistrsko delo
Organizacija: UL FFA - Fakulteta za farmacijo
Založnik: [M. Murkovič]
UDK: 616.13-004.6 (043.3)
COBISS: 4449393 Povezava se bo odprla v novem oknu
Št. ogledov: 332
Št. prenosov: 69
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Angleški jezik
Sekundarni naslov: Frequency of polymorphismsm in candidate genes in patients with peripheral arterial disease
Sekundarni povzetek: Peripheral arterial disease (PAD) is characterized by insufficient delivery of oxygenated blood to the peripheral tissues, which in most cases is caused by atherosclerosis. PAD usually affects arteries of the lower limbs. As a result of insufficient blood circulation, patients develop cramping pain in the leg muscles. These patients have a greater risk for other cardio-vascular events, because PAD is in most cases a consequence of generalized atherosclerosis. The measurement of the ankle-brancial index (ABI) is used for the diagnosis of the disease. In the case of advanced PAD (critical limb ischemia or disturbing cramping pain), revascularization should be performed. Percutaneous transluminal angioplasty (PTA) is used to treat shorter narrowing, which despite its good primary performance is limited by the development of restenosis. The development of PAD is influenced by risk factors and genetic predisposition. It has been proven that ABI is largely inherited, but it is not yet known for which genetic changes. We aimed to investigate the association between polymorphisms rs12803, rs146608 and rs13428968 of the NR4A2 gene, rs668 and rs12953 of the PECAM1 gene, rs10499563 of the IL6 gene and rs10861032 on chromosome 12 and PAD, cardio-vascular events and restenosis after PTA. To this end, we have set two surveys. In study A we enrolled 662 patients with PAD and 615 patients without PAD, while in study B there were 182 PTA patients. DNA sections, where polymorfisms are located, were multiplied with real-time PCR and genotypes were determined by allelic distrimination. We found that the studied polymorphisms are not more frequent in patients with PAD compared to peers without disease. In the patients distribution to those who suffered a cardio-vascular event and those without an event, we found that the polymorphisms rs668 of the PECAM1 gene, rs10499563 of the IL6 gene, rs10861032 on chromosome 12 and the haplotype 4 in PECAM1 are weakly associated with frequency of cardio-vascular events. GG genotype in polimorphism rs668 was associated with a 1.5-fold higher risk for a major event, TT genotype in rs10499563 was associated with a 1.6-fold higher risk for a minor event, CC genotype in rs10861032 was associated with a 2,4-fold higher risk for any event or with 2.6-fold higher risk for a minor event, and haplotype 4 in PECAM1 was associated with a 2.9-fold higher risk for any or a 3.9-fold higher risk for a minor event. Polymorphisms rs12803, rs146608 and rs13428968 of the NR4A2 gene was not associated with the frequency of cardio-vascular events. With restenosis after PTA was weakly associated polymorphisms rs668 of the PECAM1 gene and rs10499563 of the IL6 gene. GG genotype in polymorphism rs668 was associated with a 1.9-fold lower risk, and TT genotype in polymorphism rs10499563 was associated with a 2.3-fold higher risk. Polymorphisms rs12803, rs146608 and rs13428968 of the NR4A2 gene, rs12953 of the PECAM1 gene and rs10861032 on chromosome 12 was not associated with restenosis after PTA. The absence of association of some polymorphisms in candidate genes with PAD, cardio-vascular events and restenosis could be a consequence of the actual absence of association or the characteristics of the subjects. These processes are influenced by many risk factors. To determine the association of polymorphisms as independent risk factors, these factors should also be taken into account in statistical data processing. Considering that only weak links were found, findings should be confirmed on a larger group of subjects. It would also be meaningful to investigate the association between the interaction of polymorphisms with the development of PAD, cardio-vascular events and restenosis.
Sekundarne ključne besede: Periferna arterijska bolezen;
Vrsta dela (COBISS): Magistrsko delo/naloga
Komentar na gradivo: Univ. Ljubljana, Fak. za farmacijo
Strani: VIII, 47 f.
ID: 12044622