20.500.12556/RUL-174036 Povezanost polimorfizmov v genih MARC1 in PNPLA3 z nealkoholno steatozo pri mladostnikih Association of polymorphisms in MARC1 and PNPLA3 genes with non-alcoholic steatosis in adolescents Nealkoholna zamaščenost jeter (NAFLD) je najpogostejša kronična jetrna bolezen pri otrocih in mladostnikih, pri čemer njeno razširjenost dodatno povečuje globalna epidemija debelosti. Bolezen povečuje tveganje za razvoj resnejših zapletov, kot so nealkoholni steatohepatitis (NASH), fibroza in ciroza. Med ključne dejavnike pri razvoju NAFLD uvrščamo genetsko predispozicijo, pri čemer je polimorfizem PNPLA3 (rs738409) povezan z večjim tveganjem za pojav in napredovanje bolezni, medtem ko polimorfizem MARC1 (rs2642438) kaže zaščitni učinek. Večina obstoječih raziskav je bila izvedena pri odraslih, zato so podatki za pediatrično populacijo omejeni. Namen magistrske naloge je bil preučiti povezavo med pogostima polimorfizmoma PNPLA3 in MARC1 ter pojavnostjo NAFLD pri mladostnikih. V študijo je bilo vključenih 200 mladostnikov iz Črne gore, starih med 16 in 19 let. Prisotnost NAFLD smo potrdili z ultrazvočno preiskavo. Iz vzorcev polne krvi smo izolirali DNA, izvedli genotipizacijo s pomočjo hidrolizirajočih sond in analizirali povezave z biokemijskimi, antropometričnimi ter kliničnimi kazalniki. Polimorfizem MARC1 rs2642438 je bil povezan z nižjimi vrednostmi LDL-holesterola v vseh modelih, kar nakazuje zaščitni učinek variantnega alela A. Pri PNPLA3 rs738409 so nosilci variantnega alela G (CG ali GG) imeli nižji HDL-holesterol (dominantni model). V podskupini z NAFLD je bil PNPLA3 rs738409 dodatno povezan z višjim skupnim holesterolom (aditivni in dominantni model). Jetrni encimi in izračunani indeksi (HSI, FLI, PNFI) niso pokazali statistično značilnih povezav. Zaključimo lahko, da genetski dejavniki pomembno vplivajo na presnovne značilnosti, povezane z NAFLD, tudi v mladostniški populaciji Naša študija pa predstavlja pomemben prispevek k razumevanju vloge genetike pri NAFLD v adolescenci in odpira možnosti za nadaljnje raziskave genetskih označevalcev v zgodnjem odkrivanju NAFLD. Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents, with its prevalence further amplified by the global obesity epidemic. The disease increases the risk of more serious complications such as non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Among the key factors in the development of NAFLD are genetic predispositions, with the PNPLA3 (rs738409) polymorphism associated with a higher risk of disease onset and progression, whereas the MARC1 (rs2642438) polymorphism appears to have a protective effect. Most existing studies have been conducted in adults; consequently, data on the pediatric population is limited. The aim of this Master’s thesis was to investigate the association between common PNPLA3 and MARC1 polymorphisms and the occurrence of NAFLD in adolescents. The study included 200 adolescents from Montenegro, aged 16–19 years. NAFLD was diagnosed by ultrasound examination. DNA was isolated from whole blood samples, genotyping was performed using hydrolysis probes, and associations with biochemical, anthropometric, and clinical parameters were analyzed. The MARC1 rs2642438 polymorphism was associated with lower LDL-cholesterol levels across all genetic models, suggesting a protective effect of the A allele. For PNPLA3 rs738409, carriers of the G allele (CG or GG) had lower HDL-cholesterol (dominant model). In the subgroup with NAFLD, PNPLA3 rs738409 was additionally associated with higher total cholesterol (additive and dominant models). No statistically significant associations were observed for liver enzymes or calculated indices (HSI, FLI, PNFI). In conclusion, genetic factors significantly influence metabolic characteristics related to NAFLD in the adolescent population. This study provides an important contribution to understanding the role of genetics in pediatric NAFLD and highlights the need for further research on genetic markers for the early detection of NAFLD. NAFLD mladostniki PNPLA3 MARC1 genetika NAFLD adolescents PNPLA3 MARC1 genetics true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2025-09-26 08:45:04 2025-09-26 08:45:12 2025-11-15 03:40:13 0000-00-00 00:00:00 2025 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 2026-09-25 119171 30080.pdf 30080.pdf 1 A935E2B94E9F6602B755FD24C2441EE8 b837a26cb43ef9eee7b4144bf27263f246164dec7ee0f800f6c5bf7d9378ed54 2acb9ec5-9aa4-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=218773 Fakulteta za farmacijo 0 0 0