Title UTJECAJ GENA ZA TRANSFERIN I TRANSFERINSKI RECEPTOR U RAZVOJU MULTIPLE SKLEROZE Title (english) ASSOCIATION OF TRANSFERRIN AND TRANSFERRIN RECEPTOR GENE WITH MULTIPLE SCLEROSIS Author Anja Iskra Mentor Nada Starčević-Čizmarević (mentor)Committee member Jadranka Vraneković (predsjednik povjerenstva)Committee member Smiljana Ristić (član povjerenstva)Committee member Nada Starčević-Čizmarević (član povjerenstva)Granter University of Rijeka Defense date and country 2018-07-05, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Scientific / art field, BIOMEDICINE AND HEALTHCARE Abstract Multipla skleroza je upalna autoimuna bolest CNS karakterizirana upalnom destrukcijom mijelina i oštećenjem aksona. Prema dosadašnjim spoznajama bolest je uzrokovana interakcijom okolišnih faktora i genetske predispozicije iako je točan uzrok MS još uvijek nepoznat.
Ţeljezo je prisutno u mozgu uz vrlo vaţnu ulogu normalnog funkcioniranja neurona, ali njegova akumulacija u mozgu moţe biti i štetna. Neravnoteţa ţeljeza u organizmu moţe dovesti do nakupljanja ţeljeza u sivoj tvari mozga MS bolesnika koje je utvrĎeno magnetskom rezonancijom (MR) te se smatra da preopterećenje ţeljezom moţe utjecati i na samu bolest. Ţeljezo se u organizmu prenosi pomoću TF koji se veţe na TFRC što je značajan način unosa ţeljeza u stanicu mozga. Stoga je cilj ovog istraţivanja analizirati distribuciju genotipova i alela za TF C1/C2 i TFRC S142G polimorfizme kod osoba oboljelih od MS i procijeniti utjecaj TF i TFRC gena u podloţnosti za MS te utvrditi moguću povezanost s tijekom bolesti i kliničkim karakteristikama (dob nastupa bolesti, trajanje bolesti, EDSS i PI).
U istraţivanje je uključeno 323 osoba oboljelih od MS (228 ţena i 95 muškaraca) od toga njih 107 iz područja većeg rizika (Gorski kotar i centralna Istra) i 216 iz područja niţe prevalencije MS (populacije Hrvatske) s dijagnostički potvrĎenom MS prema revidiranim McDonaldovim kriterijima . Kontrolna skupina sastoji se od 323 zdravia ispitanika (228 ţena i 95 muškaraca) usklaĎena prema spolu i geografskoj regiji s bolesnicima. Provedena je analiza TF C1/C2 polimorfizma postupkom PCR-RFLP, dok je analiza TFRC S142G polimorfizma provedena postupkom Real-time PCR.
Dobiveni rezultati pokazali su podjednaku distribuciju TF i TFRC genotipova kod oboljelih od MS i to kod PP, SP i RR tijeka bolesti te se učestalost TF i TFRC genotipova i alela kod oboljelih od MS nije statistički značajno razlikovala ni od učestalosti kod kontrolne skupine (p>0,05). TakoĎer, distribucija TF i TFRC genotipova nije se statistički značajno razlikovala (p>0,05) izmeĎu oboljelih od MS i kontrolne skupine unutar ţarišta, kao ni kod oboljelih i zdravih ispitanika izvan ţarišta. Statističkom analizom povezanosti kliničkih karakteristika s distribucijom TF i TFRC genotipova (dob nastupa bolesti, trajanje bolesti, EDSS i PI) statistički značajna razlika utvrĎena je s obzirom na dob nastupa bolesti za različite TF genotipove (p=0,0007), kao i u distribuciji TFRC genotipova takoĎer prema dobi nastupa (p=0, 0241).
Iz dobivenih rezultata moţemo zaključiti da analizirani polimorfizmi TF i TFRC gena nemaju ulogu u podloţnosti za MS. Analiza TF C1/C2 i TFRC S142G polimorfizama u odnosu na kliničke parametre MS pokazuje njihov mogući utjecaj na raniju pojavnost bolesti.
Abstract (english) Multiple sclerosis is an autoimmune inflammatory disease of the CNS characterised by demyelination and axonal degeneration. Multiple sclerosis causes are unkown, however evidence suggests that the condition may result from a combination of genetics and enviromental factors.
Iron is essential in neuronal cell life, yet brain iron accumulation can be toxic. Iron imbalance in the body can lead to the iron builds up in the gray matter brain determined by magnetic resonance (MR) and considered iron overload may also MS affects. TFRC is a carrier protein for TF and it is needed for the import of iron into the brain cell. Tha aim of this is analysis the distribution of genotypes and allelic frequencies of the TF C1/C2 polymorphism and TFRC S142G polymorphism in MS patients, evaluate the association of TF and TFRC gene with MS and possible coherence with disease cource and clinical characteristics (age at the onset, disease duration, EDSS, PI).
The study included 323 patients (228 women and 95 men), 107 from high risk area for MS (Gorski kotar and central Istra), 216 from other parts of the Republic of Croatia with established diagnosis according to McDonald criteria and 323 patients (228 women and 95 men) blood donors as control. The control and MS patient groups were compared. The analysis of TF C1/C2 polymorphism was conducted by PCR-RFLP, analysis of TFRC S142G polymorphism was conducted by Real-time PCR.
Result have not shown statistically significant different (p>0,05) in frequency of TF C1/C2 and TFRC alleles and genotypes between patients and control, and neither between patients and control from high risk area. Clinical characteristics of multiple sclerosis (disease duration, EDSS, PI) did not show significant differences (p>0,05) in patients and control group but age at the onset was show significant differences of TF genotype (p=0,0007) and TFRC genotype (p=0, 0241).
Finally, the result showed that genotype of TF and TFRC have no role in the susceptibility to MS. Analysis of TF C1/C2 and TFRC S142G polymorphism in regards to clinical characteristics of MS shows their possible influence on the earlier age at the onset of disease.
Keywords
multipla skleroza
transferin
transferinski receptor
genski polimorfizam
željezo
Keywords (english)
multiple sclerosis transferrin
transferrin receptor
genetic polymorphis
iron
Language croatian URN:NBN urn:nbn:hr:184:279732 Study programme Title: Study of Sanitary Engineering Type of resource Text File origin Born digital Access conditions Access restricted to students and staff of home institution Terms of use Repository Repository of the University of Rijeka, Faculty of Medicine Created on 2018-12-07 10:42:51
