Jovičić Pavlović, Svetlana, 1963- srp Novaković, Ivana, 1961- Jovanović, Dijana, 1960- Ristanović, Momčilo, 1968- Petrović, Lada, 1967- UVOD: Hronična bubreţna bolest (HBB) je nezavistan faktori rizika za kardiovaskularne bolesti. Cilj ovog rada je da se ispita efekat polimorfizama gena za homocistein MTHFR 677C>T, MTHFR 1298 A>C, interleukin 6 -174G>C, interleukin 10 -1082G>A i -819T>C i fetuin 742 C>T i 766 C>G na koncentracije homocisteina, IL-6 i IL-10, fetuina i na rane i kasne pokazatelje ateroskleroze, pojavu kalcifikacija na koronarnim arterijama (KKA) i preţivljavanje bolesnika. transplantiranim bubregom (TX). U studiji za IL-6 i IL -10 228 bolesnika (77 HD i 55 na peritoenumskoj dijalizi), a za fetuin 88 (46 sa HBB i 42 Tx) i kontrolnoj grupi 28 zdravih osoba. Odredjivani su polimorfizmi u genima PCR metodom, biohemijske analize, CRP, amiloid A, fetuin-A, homo-cistein, IL-6 i IL-10. Merena je debljine intima medije (IMD) karotidnih arterija i prisustvo plaka, a skor kalci-fikacija multislajsnom tomografijom. REZULTATI: Bolesnici sa MTHFR 677 CT i TT genotipom su imali više vrednosti Hcy, ali bez statističke značajnosti. Ho-mozigoti sa genotipom IL-6 -174CC su imali značajno više koncentracije IL-6 (6,4pg/ml), u odnosu na -174GC+GG genotipove (3,1pg/ml, p=0,30). Koncentracije IL-10 nisu razlikovale prema genotipovima IL-10 -1082G>A i -819T>C. Homozigoti sa genotipom u genu za fetuin 742TT i 766GG su imali najniţe koncentracije fetuina-A (p=0,02). Aterosklerotski plak na karotidnim arterijama je imalo 47% bolesnika. IMD i izraţenost plaka nije se razlikovala medju MTHFR genotipovima. Ispitanici sa plak skorom 1-3 su bili značajno stariji, češće su imali hipertenziju, viši C reaktivni protein i kreatinin, a najznačajniji prediktor je bila starost (B=0,133; p<0,001, OR =1,14). KKA je imalo 46,5 % bolesnika. Bolesnici sa fetuinom-A <0,437g/l su imali češće KKA i veći skor. U univari-jantnoj analizi prediktori KKA su bili starost, nivo fetuina-A i polimorfizam u genima za fetuin, a u multivari-jantoj analizi starost (OR=0,17) i fetuin-A (OR=0,17). Heterozigoti MTHFR 677CT su imali lošije preţivljavanje u odnosu na ostale MTHFR genotipove. Značajno veći mortalitet su imali bolesnici sa IL-6 -174CC genotipom (95%CI 20,0-32,2) u odnosu na GC i GG genotip (hi kvadrat 11,398; p=0,003), različiti IL-10 genotipovi nisu značajno uticali na preţivljavanje. Najznačajniji prediktor za smrtnost su bili koncentracija IL-6, CRP, albumin, kt/v i polimorfizam u genu za IL-6 -174G>C. Petogodišnje preţivljavanje bolesnika bez mutacije u genu za fetuin 742C>T je bilo 100%, kod bolesnika sa mutacijom 81%, a ukoliko su imali i povišene vrednosti C reaktivnog proteina 50%. ZAKLJUčAK: Ispitivanja u ovom radu nisu pokazala da je polimorfizam u genu za MTHFR značajno povezan sa koncentracijom homocisteina, niti sa parametrima ateroskleroze, heterozigoti MTHFR 677CT su imali lošije preţivljavanje. Polimorfizam IL-6 -174G>C je bio povezan sa koncentracijama IL-6, homozigoti 174CC su im-ali značajno više koncentracije IL-6 i lošije preţivljavanje. Polimorfizmi u genu za fetuin su bili udruţeni sa niţim koncentracijama fetuina-A u krvi i sa lošijim preţivljavanjem. Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. The aim of this study was to examine the effect of gene polymorphisms for homocysteine MTHFR 677C> T, MTHFR 1298 A> C, interleukin 6 -174G> C, interleukin 10 -1082G> A and -819T> C for fetuin 742 C> T and 766 C > G on con-centrations of homocysteine, IL-6 and IL-10, fetuin and on early and late indicators of atherosclerosis, the oc-currence of coronary artery calcifications (COA) and patient survival. METHODS: The Hcy study included 188 patients, 82 treated with hemodialysis (HD) and 106 with kidney transplantation (TX). In the study for IL-6 and IL-10 228 were included (77 HD and 55 on peritoneum dialysis), and for fetuin 88 (46 with HBB and 42 Tx) and the control group of 28 healthy individuals. Polymorphisms in genes were determined by PCR, biochemical analysis, CRP, amyloid A, fetuin-A, homo-cysteine, IL-6 and IL-10. The thickness of the intimate media (IMD) of the carotid arteries and the presence of plaque were measured, and the score was calcified by multislice tomography. RESULTS: Patients with MTHFR 677CT and TT genotype had higher Hcy values, but no statistical signific-ance. Homozygotes with genotype IL-6 -174CC had significantly higher IL-6 concentrations of 6.4pg / ml, compared to -174GC + GG genotypes (3.1pg / ml, p = 0.30). IL-10 concentrations did not differ according to IL-10 genotypes -1082G> A and -819T> C. Homozygotes for mutations in the fetuin gene 742TT and 766GG had the lowest concentrations of fetuin-A (p = 0.02). IMD and plaque expression did not differ among MTHFR genotypes. Subjects with a plaque score of 1-3 were significantly older, more likely to have hypertension, higher C-reactive protein and creatinine, and the most sig-nificant predictor was age (B = 0.133; p <0.001, OR = 1.14). Patients with fetuin-A <0.437 g / l had more frequent CCA and a higher score. In the univariate analysis, the predictors of CCA were age, fetuin-A level, and polymorphism in fetuin genes, and in the multivariate analysis, age (OR = 0.17) and fetuin-A (OR = 0.17). Heterozygotes of MTHFR 677CT had poorer survival compared to other MTHFR genotypes. Patients with IL-6 -174CC genotype had significantly higher mortality (95% CI 20.0-32.2) compared to GC and GG genotype (chi square 11.398; p = 0.003), different IL-10 genotypes were not significantly affected to survival. The most im-portant predictors for mortality were IL-6 concentration, CRP, albumin, kt / v, and IL-6 -174G> C gene poly-morphism. The five-year survival of patients without mutation in the fetus 742C> T gene was 100%, in patients with mutation 81%, and in patients with elevated reactive protein C values 50%. CONCLUSION: The studies in this paper did not show that polymorphism in the MTHFR gene was significant-ly associated with homocysteine concentration or atherosclerosis parameters, MTHFR 677CT heterozygotes had poorer survival. The IL-6 -174G>C polymorphism was associated with IL-6 concentrations, mutation homozy-gotes had significantly higher IL-6 concentrations and poorer survival. Polymorphisms in the fetuin gene 742 C>T and 766C>G were associated with lower blood concentrations of fetuin-A and poorer survival. Medicina - Nefrologija / Medicine - Nephrology Datum odbrane: 26.09.2022. info:eu-repo/semantics/bachelorThesis https://phaidrabg.bg.ac.rs/o:27299 cobiss:82004489 thesis:8919 http://creativecommons.org/licenses/by-nc-nd/3.0/at/legalcode 60 str. 2838726 bytes Ispitivanje povezanosti genskih polimorfizama sa kardiovaskularnim bolestima kod bolesnika sa terminalnom bubrežnom slabosti : doktorska disertacija 2022 OSNO - Opšta sistematizacija naučnih oblasti, Nefrologija OSNO - Opšta sistematizacija naučnih oblasti, Nefrologija genski polimorfizmi, kardiovaskularne bolesti, ateroskleroza, hronična bubrezna bolest, homocistein, inflamacija, fetuin-A, kalcifikacije krvnih sudova gene polymorphisms, cardiovascular diseases, atherosclerosis, chronic kidney disease, homocysteine, inflamation, fetuin A, coronary artery calcifications 616.61-008.64:616.1(043.3)