Uticaj genskog polimorfizma za angiotenzin konvertujući enzim, matriksnu metaloproteinazu 3, endotelnu azot oksid sintetazu, interleukine 6 i 10 i faktor nekroze tumora na kardiovaskularni morbiditet i mortalitet bolesnika na hemodijalizi
Influence of gene polymorphisms for angiotensine converting enzyme, matrix metalloproteinase 3, endothelial nitric oxidase, interleukins 6 and 10 and tumor necrosis factor on cardiovascular morbidity and mortality in hemodialysis patients
Докторанд
Tošić Dragović, Jelena S.Ментор
Dimković, NadaЧланови комисије
Ležaić, VišnjaIvanović, Branislava
Petrović, Dejan
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Метаподаци
Приказ свих података о дисертацијиСажетак
Kardiovaskularne bolesti (KVB) su glavni uzrok morbiditeta (Mb) i mortaliteta (Mt)
bolesnika u terminalnoj fazi hronične bubreţne slabosti (HBS). Godišnja stopa Mt usled KVB
iznosi 9%, što je 10-20 puta više nego u opštoj populaciji nakon prilagoĎavanja za starost, pol,
rasu i diabetes mellitus. Visoka incidenca smrti od infarkta miokarda kod bolesnika srednje
ţivotne dobi na hroničnoj hemodijalizi (HD) zapaţena je još ranih ’70- tih godina i objašnjena je
hipotezom o “akcelerirajućoj aterosklerozi”, koja je i danas podjednako aktuelna. Klasični faktori
rizika kao što su starija ţivotna dob, hipertenzija, dislipidemija, dijabetes melitus, fizička
neaktivnost i pušenje nisu mogli zadovoljavajuće objasniti visoku prevalencu koronarne bolesti u
HBS. Kasnija istraţivanja su pokazala da se ubrzana aterogeneza kod bolesnika sa HBS
pojavljuje usled sinergizma mehanizama koji obuhvataju malnutriciju, inflamaciju, oksidativni
stres i genetske komponente.
Zbog toga u poslednje vreme paţnju mnogi...h istraţivača privlače takozvani netradicionalni faktori
rizika, u koje se od skora pored vrednosti ukupnog homocisteina, lipoproteina a (Lp(a)), infekcija
Herpesvirusima i Chlamidiom pneumonie, ubraja i polimorfizam gena za različite proteine koji
učestvuju u genezi ateroskleroze. Tokom proteklih nekoliko godina najveći broj ovih istraţivanja
bavio se polimorfizmima za različite gene endotelne disfunkcije i gene inflamatornog odgovora
(angiotenzin konvertujući enzim (ACE) i matriksne metaloproteinaze (MMP), endotelna azot
oksid sintetaza (eNOS), interleukin-6 (IL-6), interleukin-10 (IL-10), faktor nekroze tumora
(TNF)).
Cilj ove studije bio je analiza kardiovaskularnog morbiditeta i ukupnog i kardiovaskularnog
mortaliteta u odnosu na genski polimorfizam za ACE, MMP-3, eNOS, Il-10, IL-6 i TNF kod
bolesnika koji se leče hroničnim hemodijalizama, kao i da se odredi koji od navedenih genskih
polimorfizama ima najviše uticaja na pojavu kardiovaskularnih dogaĎaja u navedenoj populaciji...
Introduction:Cardiovascular disease (CVD) is leading cause of morbidity and death in
haemodialysis patients. The risk for developing cardiovascular event is 10-20 folds higher in
patients with end stage renal desease (ESRD) than in the general population, after adjustment for
age, gender, race and diabetes mellitus. High mortality rate in hemodialysis patients was
observed in early ’70ies and was explained with “accelerated atherosclerosis” hypothesis.
Traditional risk factors (elderly patients, hypertension, dislipidaemia, diabetes, sedentary life
style and smoking), could not explain high prevalence of cardiovascular disease in haemodialysis
patients. That why recent reports have suggested a role of non-traditional risk factors in
pathogenesis of CVD, such as malnutrition, inflammation, oxidative stress, homocysteine levels,
Lp(a), infections with Herpes and Chlamidia pneumoniae and gene polymorphism of proteins
involved in pathogenesis of atherosclerosis. For the last few years inve...stigators were focused on
genes of endothelial dysfunction (ACE, MMP3, eNOS) and genes of inflammatory response (Il/6,
IL/10, TNF). Gene polymorphism includes egzistance of two or more variant of one gene when
frequency of its rarest allele in population is more than 1%.
The aim of this study was to analyse cardiovascular morbidity and overall and cardiovascular
mortality regarding the gene polymorphisms for ACE, MMP3, eNOS, IL-10, IL-6 and TNF in
patients on chronic dialysis and to detect which gene polymorphism has the highest impact on
cardiovascular events in henodialysis patients.
Methods: The study included 315 patients on regular hemodialysis longer than 6 months in
University Clinical Center „Zvezdara“, Belgrade. All patients had 3 dialysis sessions weekly in
duration of 4/5 hours. Venous blood sample was collected in midweek dialysis and was sent for
genotyping...