Vloga polimorfizmov v genih za izbrane metiltransferaze pri nastanku orofacialnih shiz : magistrski študijski program Laboratorijska biomedicin

Štruc, Tina (author), Karas Kuželički, Nataša (mentor), Šmid, Alenka (co-mentor)

Orofacialne shize so ene najpogostejših prirojenih razvojnih nepravilnosti. So razvojne anomalije obraza in ustne votline s kompleksno etiologijo, saj nanje vplivajo demografski, okoljski in genetski dejavniki. Za normalen embrionalni razvoj plodu so pomembni folati, ki sodelujejo pri sintezi nukleotidov, remetilaciji homocisteina in bioloških reakcijah metilacije. Ker pa je vpliv genetskih dejavnikov na nastanek shiz še dokaj nejasen, smo v magistrski nalogi želeli raziskati vpliv pogostih polimorfizmov izbranih metiltransferaz, ki delujejo v omenjenih procesih (BHMT rs3733890_G>A, GNMT rs10948059_C>T in DNMT3B rs2424913_C>T) na razvoj shiz. Vključili smo tudi demografske in okoljske dejavnike tveganja, ki bi lahko vplivali na pojavnost le-teh. V preiskovalno skupino smo vključili 179 oz. 58 parov mater in njihovih otrok rojenih z orofacialno shizo, ter v kontrolno skupino 200 parov oz. 192 mater in zdravih otrok. Ugotovili smo, da imajo matere, ki med nosečnostjo uživajo pripravke s folno kislino, multivitaminske dodatke ter z metioninom bogato hrano, zmanjšano tveganje za rojstvo otroka z orofacialno shizo. Matere kadilke, kot tudi matere, ki so v prvem trimesečju izpostavljene povišani telesni temperaturi nad 38°C, imajo povečano tveganje za razvoj orofacialne shize pri otroku. Ker je bila družinska anamneza v naši raziskavi največji dejavnik tveganja, smo genetski vpliv izbranih polimorfizmov ugotavljali v populaciji mater in otrok, s pozitivno družinsko anamnezo. Dokazali smo, da prisotnost mutiranih alelov BHMT in GNMT pri otroku poveča tveganje za nastanek shize. Tveganje se še poveča, če so mutirani aleli BHMT ali GNMT hkrati prisotni pri materi in otroku. Večje skupno število mutiranih alelov na treh preiskovanih lokusih pri materi in otroku poveča verjetnost za nastanek shiz, kar kaže na poligensko dedovanje prirojenih okvar.

• Language: Slovenian
• Keywords: orofacialne shize, polimorfizmi, beta homocistein metiltransferaza, gen za N-metiltransferazo, DNA metilstransferaza, genetski dejavniki
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: FFA - Faculty of Pharmacy
• Place of publishing: Ljubljana
• Publisher: [T. Štruc]
• Year: 2016
• Number of pages: IX, 74 f.
• PID: 20.500.12556/RUL-87338
• UDC: 577.1(043.3)
• COBISS.SI-ID: 4110705
• Publication date in RUL: 08.12.2016

Secondary language

• Language: English
• Title: Influence of polymorphisms in selected methyltransferase genes on cleft lip and/or palate development

Abstract

Orofacial clefts are one of the most common congenital abnormalities. These birth anomalies affecting the lips and oral cavity have complex etiology with demographic, environmental and genetic risk factors influencing their development. Folates are important for normal embryological development, because of their involvement in the synthesis of nucleotides, homocysteine remethylation and biological methylation reactions. Since the influence of genetic factors on the occurrence of clefts is still quite unclear, the aim of this Master's thesis was to explore the influence of polymorphisms in selected methyltransferase genes (BHMT rs3733890_G>A, GNMT rs10948059_C>T and DNMT3B rs2424913_C>T) previously mentioned processes. We also investigated the influence of selected demographic and environmental risk factors. The case group included 179 or 58 pairs of mothers and their children with orofacial cleft, and the control group 200 or 192 pairs of mothers and healthy children. Mothers who were taking folic acid supplements, multivitamins and methionine rich food during the pregnancy had reduced risk of having a child with oral cleft. Maternal smoking and maternal fever above 38° C in the first trimester of pregnancy increased the risk of orofacial cleft. Since family history was the greatest risk factor we decided to observe the influence of selected polymorphisms in the population of mother and child pairs with positive family history. We found out that the presence of mutant alleles of BHMT and GNMT in a child increases the risk of developing a cleft. The risk is further increased, if the mutated alleles in BHMT or GNMT are present in the mother and child concurrently. Higher total number of mutant alleles at investigated three loci in mother and child increases the likelihood for the occurrence of cleft, suggesting a polygenic inheritance of these congenital defects.