Polimorfizam gena TPMT u bolesnika s upalnom bolesti crijeva

master's thesis

• Title (english): DETERMINATION OF GENETIC POLYMORPHISM OF TPMT GENE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE BY TAQMAN ASSAY
• Author: Nikolina Zoko
• Mentor: Nada Božina (mentor)
• Mentor: Inga Marijanović (mentor)
• Committee member: Inga Marijanović (predsjednik povjerenstva)
• Committee member: Nada Božina (član povjerenstva)
• Committee member: Željka Vidaković-Cifrek (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2012-02-10, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

U liječenju upalne bolesti crijeva koriste se tiopurinski lijekovi čija se doza često mora smanjiti ili se terapija mora prekinuti jer neki pacijenti razvijaju nuspojave. Redovito se provode enzimski i genetički testovi da bi se nuspojave detektirale u ranoj fazi. Kako se tiopurini moraju unutarstanično promijeniti da bi imali terapijski učinak, proučavaju se enzimi uključeni u njihov metabolizam. Jedan od tih enzima je tiopurinmetiltransferaza (TPMT). Postoje značajne interindividualne razlike u aktivnosti tog enzima koje su uglavnom posljedica polimorfizma u jednoj bazi u genu TPMT od kojih se u rutinskoj kliničkoj praksi ispituju TPMT*2, TPMT*3A i TMPT*3C. Da bi se dijagnosticirala deficijencija TPMT koriste se metode genotipizacije, kao što je TaqMan® metoda lančane reakcije polimeraze u stvarnom vremenu. Prema rezultatima dobivenima u ovom istraživanju može se zaključiti da je alel TPMT*3A najčešći mutirani alel u ispitivanoj hrvatskoj populaciji, što korelira s nalazom za ostale bjelačke populacije. Potrebna su dodatna istraživanja kako bi se u cijelosti razumjela regulacija aktivnosti TPMT.

Abstract (english)

Thiopurine drugs are used in the treatment of inflammatory bowel disease. Their dose often has to be reduced or therapy has to be canceled because some patients develop adverse drug reactions. Blood tests and genetic tests are regularly carried out to detect side effects at an early stage. Since thiopurines need to be intracellularly changed to have a therapeutic effect, the enzymes involved in their metabolism are being studied and one of them is thiopurine methyltransferase (TPMT). Significant interindividual differences which exist in activity of this enzyme are mostly a consequence of single nucleotide polymorphisms found in the TPMT gene and TPMT*2, TPMT*3A and TMPT*3C alleles are the ones that are studied in routine clinical trials. Different genotyping methods are used to diagnose TPMT deficiency, such as TaqMan® real time-PCR method. According to the results obtained in this study we can conclude that the TPMT*3A allele is the most common mutant allele among the Croatian population, which correlates with results of other Caucasian populations. Further studies are needed to fully understand the regulation of TPMT activity.

• Keywords: AZA; 6-MP; 6-TG; 6-TGN; nuspojave; doziranje; TaqMan® metoda
• Keywords (english): AZA; 6-MP; 6-TG; 6-TGN; adverse drug reactions; dosing; TaqMan® method
• Language: croatian
• URN:NBN: urn:nbn:hr:217:489319
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-05-02 12:28:35