o:29359 Korelacija odabranih genetičkih polimorfizama i komplikacija dugotrajne primene levodope kod osoba koje boluju od Parkinsonove bolesti doktorska disertacija The correlation of selected genetic polymorphisms and complications of long-term use of levodopa in individuals with Parkinson's disease : doctoral dissertation sr Polimorfizmi u različitim genima koji učestvuju u metabolizmu i transportu dopaminaproučavani su u vezi sa pojavom neželjenih efekata primene levodope kod osoba koje bolujuod Parkinsonove bolesti (PB), ali još uvek ne postoje konzistentni podaci. Naš cilj je bio daispitamo korelaciju između odabranih polimorfizama COMT, DRD2, ANKK1 i DAT gena ipojave komplikacija dugotrajne primene levodope poput diskinezija, halucinacija i psihoze. Ustudiju je bilo uključeno 234 bolesnika koji boluju od idiopatske PB, koji su na početkupojave motornih simptoma imali ≥40 godina starosti i koji su bar 2 godine bili na terapijilevodopom. Svaki pacijent je podvrgnut detaljnom neurološkom pregledu, kognitivnoj ibihejvioralnoj proceni. Vršena je genotipizacija za tri polimorfizma u DRD2 genu (rs2283265,rs1076560, rs6277), dva polimorfizma u ANKK1 genu (rs1800497 i rs2734849) i jedanpolimorfizam u COMT genu (Val158Met, rs4680). Takođe, određivan je broj ponovaka u3'UTR regionu DAT gena. Od ukupnog broja ispitanika, diskinezije su bile prisutne kod51,3%, halucinacije su se javile kod 41,9%, a psihoza kod 43,2% obolelih ispitanika.Homozigoti za alel niske COMT aktivnosti bili su udruženi sa značajno većom učestalošćudiskinezija. Polimorfizam rs2734849 ANKK1 gena indukovao je vulnerabilnost za pojavuhalucinacija kod obolelih ispitanika. Nosioci GG genotipa rs2734849 ANKK1 gena i AAgenotipa rs6277 DRD2 gena imali su 2,2, odnosno 2,3 puta veći rizik od pojave psihoze uPB. Pored prethodne izloženosti dopaminergičkim lekovima, motornog statusa, depresije ianksioznosti, kao dobro utvrđenih kliničkih faktora rizika za razvoj psihoze, GG rs2734849ANKK1 mogao bi, takođe, biti faktor od uticaja, što zahteva potvrdu u budućimlongitudinalnim studijama. Polymorphisms in genes involved in dopamine metabolism and transport have been studiedconcerning the occurrence of side effects of levodopa in patients with Parkinson's disease(PD), but there is no consistent data. We aimed to examine the correlation between selectedpolymorphisms of the COMT, DRD2, ANKK1, and DAT genes and the occurrence ofcomplications of long-term use of levodopa such as dyskinesias, hallucinations, andpsychosis. The study included 234 PD patients who were ≥40 years old at disease onset andon levodopa therapy for at least two years. Each patient underwent a detailed neurologicalexamination and cognitive and behavioral assessment. Genotyping of three polymorphisms inthe DRD2 gene (rs2283265, rs1076560, rs6277), two polymorphisms in the ANKK1 gene(rs1800497 and rs2734849), and one polymorphism in the COMT gene (Val158Met, 151rs4680) was done. Also, a variable number of tandem repeats polymorphism in the 3’UTRregion of the DAT gene was determined. Of the participants, dyskinesias were present in51.3%, hallucinations occurred in 41.9%, and psychosis in 43.2% of patients. Homozygotesfor the allele of low COMT activity were associated with a significantly higher incidence ofdyskinesias. The rs2734849 ANKK1 gene polymorphism induced vulnerability tohallucinations in PD patients. Carriers of GG genotype rs2734849 ANKK1 gene and AAgenotype rs6277 DRD2 gene had a 2.2 and 2.3 times higher risk of developing psychosis inPD, respectively. Besides previous exposure to dopaminergic drugs, impairment of motorstatus, depression, and anxiety, as well-established clinical risk factors for PDP development,GG rs2734849 ANKK1 could also be a contributing factor that requires addressing by futurelongitudinal studies. Medicina - Farmakologija / Medicine- Pharmacology Datum odbrane: 15.07.2022. Parkinsonova bolest, levodopa, genetički polimorfizmi, COMT, DRD2, ANKK1, DAT geni Parkinson's disease, levodopa, genetic polymorphisms, COMT, DRD2, ANKK1, DAT genes 615.21:616.858(043.3) 91552100 71325449 91552101 9090 2023-05-12T09:13:09.053Z 45 no 46 Branislava, 1977- Radojević 88008457 2022 63 mentor Miroslav M., 1973- Savić 12866407 2022 63 mentor Nataša, 1966- Dragašević-Mišković 12712807 2022 63 član komisije Ivan, 1979- Jančić 20112743 2022 63 član komisije Marina, 1959- Svetel 12535911 2022 63 član komisije Igor, 1973- Petrović 13784935 2022 134, [26] str. 5083482 http://phaidrabg.bg.ac.rs/o:29359 no yes 1 2023-05-12T09:13:09.320Z 70 11 1067094 Parkinsonova bolest, levodopa, genetički polimorfizmi, COMT, DRD2,ANKK1, DAT geni Parkinson's disease, levodopa, genetic polymorphisms, COMT, DRD2, ANKK1,DAT genes 615.21:616.858(043.3) 1738 11A13 2022