Povezanost neurorazvojnih poremećaja sa varijantama gena za laktazu, humani antigen leukocita i receptor vitamina D, kao i sa prisustvom opioidnih peptida u urinu i crevnom disbiozom
The association of neurodevelopmental disorders with genetic variants linked with lactose intolerance, human leukocyte antigen and vitamin d receptor, as well as the presence of opioid peptides in the urine and intestinal dysbiosis
Докторанд
Bojović, KatarinaМентор
Ignjatović, ĐurđicaЧланови комисије
Savić-Pavićević, DušankaTolinački, Maja
Stanković, Biljana
Zeljić, Katarina
Метаподаци
Приказ свих података о дисертацијиСажетак
Nutritivne deficijencije, gastrointestinalne smetnje i intolerancija na hranu često su opisivane
kod dece sa neurorazvojnim poremećajima (eng. neurodevelopmental disorder, NDD).
Pretpostavljeno je da opioidni molekuli, poreklom od proteina kazeina i glutena mogu dovesti do
nastanka nekih neuropsihijatrijskih simptoma. S obzirom da su do sada u literaturi povišene
koncetracije ovih peptida u urinu opisivane kod pacijenata sa autizmom, ali ne i drugim formama
NDD, prvi cilj ove teze bio je proveriti da li kod NDD pacijenata postoji povišen nivo kazo- i gluten
egzorfina u urinu metodom tečne hromatografije visokih performansi. Kako je glavni preduslov da
navedeni peptidi dospeju u cirkulaciju povećana propustljivost crevnog epitela, istraživanje je dalje
bilo usmereno na ispitivanje učestalosti genetičkih varijanti asociranih sa celijačnom bolešću (HLADQ)
i laktoznom intolerancijom (LCT-13910C>T) metodama baziranim na PCR analizi i ispitivanju
promena u sastavu crevne mikrobiote... metodom gel elektroforeze u denaturišućem gradijentu. Kod
većine pacijenata sa NDD detektovan je nedostatak vitamina D, zbog čega je metodama PCR analize
ispitivana učestalost genetičke varijante VDR FokI, koja je u literaturi dovođena u vezu sa autizmom.
Rezultati istraživanja pokazali su povećanu koncentraciju analiziranih peptida u urinu NDD
pacijenata koja nije bila asocirana sa genetičkim markerima za celijačnu bolest i laktoznu
intoleranciju. Značajno viša učestalost genotipa VDR FokI CC ("FF") je pokazana kod pacijenata sa
dečijim autizmom u odnosu na zdrave kontrole, ali i ostale grupe NDD pacijenata. U grupi pacijenata
uočena je manja zastupljenost i smanjen diverzitet bakterija koje čine normalnu crevnu mikrobiotu,
kao i veća zastupljenost potencijalno patogenih bakterija.
Nutritional deficiencies, gastrointestinal disturbances, and food intolerance are frequently
observed in children with neurodevelopmental disorders (NDD). It was hypothesized that opioid
molecules, originally derived from the protein of casein and gluten, may induce some of the
neuropsychiatric symptoms. Since the elevated levels of these peptides in the urine have so far been
described in medical literature in patients with autism, but not in other forms of NDD, the first goal
of this thesis was to check whether the NDD patients have elevated levels of casein- and gluten
exorphins in the urine using the method of High performance liquid chromatography. Since increased
intestinal permeability is the main precondition for the presence of these peptides in circulation, the
research was further directed to examine the frequency of genetic variants associated with celiac
disease (HLA-DQ) and lactose intolerance (LCT-13910C) methods based on PCR analysis and to
examine changes in ...the composition of gut microbiota. Given that the vitamin D deficiency was
detected in most of the NDD patients, the frequency of the genetic variant VDR FokI, which has been
linked to autism in the medical literature, was examined by methods based on PCR analysis.
Results indicated that increased concentrations of analized peptides observed in NDD patients
were not associated with genetic predictors for celiac disease or lactose intolerance. A significantly
higher incidence of the Fokl CC (FF) genotype in patients with childhood autism was noted compared
to healthy control and other groups of NDD patients. Within the patients group a lower incidence and
diversity of common commensal bacteria was noted, as well as the higher incidence of potentially
harmful bacteria.