Naslov (srp)

Molekularno-genetička analiza akvaporina 4 i korelacija sa kliničkim karakteristikama obolelih od neuromijelitis optika spektra bolesti : doktorska disertacija

Autor

Andabaka, Marko, 1990-

Doprinosi

Novaković, Ivana, 1961-
Mesaroš, Šarlota, 1967-
Drulović, Jelena, 1960-
Pekmezović, Tatjana, 1964-
Peterlin, Borut

Opis (srp)

multifaktorijalni mehanizmi interakcije genetičkih činilaca i faktora spoljašnje sredine.Ciljevi: Analiza gena za akvaporin 4 (AQP4) kod obolelih od NMOSB i multiple skleroze(MS), analiza čitavog egzoma obolelih od NMOSB, kao i korelacija genetičkih markera sakliničkim karakteristikama osoba obolelih od NMOSB. Procena kvaliteta života obolelih odNMOSB i MS.Ispitanici i metode: Istraživanje je obuhvatilo uzorke DNK ukupno 64 pacijenata saNMOSB, 40 pacijenata sa MS, kao i 100 uzoraka zdravih osoba. Nakon amplifikacijekodirajućih regiona gena AQP4 učinjeno je njihovo sekvenciranje metodom po Sangeru.Dobijene varijante su korelisane sa kliničkim karakteristikama obolelih od NMOSB. Analizacelog egzoma (engl. Whole Exome Sequencing, WES) sprovedena je na Illumina HiSeq-2000platformi pomoću komercijalnih kitova, za svih 64 pacijenata sa NMOSB. Analiziran jeodabrani panel gena u kojima su izdvojene varijante od potencijalnog značaja u NMOSB, kaoi opterećenje ovim genima u NMOSB. Za procenu kvaliteta života obavljena je studijapreseka sa ukupno 180 ispitanika (80 NMOSB, 100 MS) primenom odgovarajućih upitnika.Rezultati: U kodirajućim regionima gena AQP4 samo za varijantu rs35248760 pokazana jestatistički značajna povezanost sa mijelitisom kod osoba sa NMOSB. Učinjenom analizomopterećenja retkim varijantama u okviru WES, nisu detektovane patogene varijante ili genirizika za razvoj NMOSB.Zaključci: Osim varijante rs35248760 u kodirajućim regionima gena AQP4 nisu detektovanedruge varijante od značaja. NMOSB predstavlja bolest sa kompleksnom genetičkomosnovom. Kvalitet života osoba sa NMOSB i MS značajno je narušen postojanjem autonomnedisfunkcije.

Opis (srp)

Medicina - Neuronauke / Medicine- Neuroscience Datum odbrane: 26.09.2024.

Opis (eng)

Introduction: In Neuromyelitis optica spectrum disorder (NMOSD) is based on complexmultifactorial mechanisms of interaction between genetic factors and environmental factors.Objectives: Analysis of the gene for aquaporin-4 (AQP4) in patients with NMOSD andMultiple Sclerosis (MS), whole exome analysis of NMOSD patients and correlation of geneticmarkers with clinical characteristics of NMOSD patients. Assessment of the quality of lifepatients with NMOSD and MS.Patients and methods: This study included DNA samples from a total of 64 patients withNMOSD, 40 patients from NMOSD, as well as 100 samples from healthy individuals. Afteramplification of the coding regions of AQP4 gene, they were sequenced by the Sanger'smethod. The obtained variants were correlated with clinical characteristics of patients withNMOSD. For all 64 patients with NMOSD whole exome sequencing (WES) analysis wasperformed on the Illumina HiSeq-2000 platform using commercial kits. A selected panel ofgenes was analyzed in which variants of potential significance in NMOSB were identified, aswell as the burden of these genes in NMOSB. To assess the quality of life, a cross-sectionalstudy was conducted with a total of 180 patients (80 NMOSD, 100 MS) using appropriatequestionnaires.Results: In the coding regions of AQP4 gene, only the rs35248760 variant showed astatistically significant association with myelitis in individuals with NMOSD. By analyzingthe burden of rare variants within WES, no pathogenic variants or risk genes for thedevelopment of NMOSD were detected.Conclusions: Besides the variant rs35248760, no other significant variants were detected inthe coding regions of the AQP4 gene. NMOSD is a disease with a complex genetic basis. Thequality of life of people with NMOSD and MS is significantly impaired by the presence ofautonomic dysfunction.

Jezik

srpski

Datum

2024

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC 3.0 AT - Creative Commons Autorstvo - Nekomercijalno 3.0 Austria License.

http://creativecommons.org/licenses/by-nc/3.0/at/legalcode

Predmet

OSNO - Opšta sistematizacija naučnih oblasti, Neurologija. Neuropatije

Neuromyelitis optica spectrum disorder, Multiple sclerosis, clinical characteristics, aquaporin 4 gene, genetic basis, quality of life, dysautonomia, neuroimmunology, neurogenetics

OSNO - Opšta sistematizacija naučnih oblasti, Neurologija. Neuropatije

neuromijelitis optika spektar bolesti, multipla skleroza, kliničke karakteristike, gen za akvaporin 4, genetička osnova, kvalitet života, disautonomija, neuroimunologija, neurogenetika.

616.8-009:577.2(043.3)