8 research outputs found

    The correlation of selected genetic polymorphisms and complications of long-term use of levodopa in individuals with Parkinson's disease

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    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

    The correlation of selected genetic polymorphisms and complications of long-term use of levodopa in individuals with Parkinson's disease

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    Polimorfizmi u različitim genima koji učestvuju u metabolizmu i transportu dopamina proučavani su u vezi sa pojavom neželjenih efekata primene levodope kod osoba koje boluju od Parkinsonove bolesti (PB), ali još uvek ne postoje konzistentni podaci. Naš cilj je bio da ispitamo korelaciju između odabranih polimorfizama COMT, DRD2, ANKK1 i DAT gena i pojave komplikacija dugotrajne primene levodope poput diskinezija, halucinacija i psihoze. U studiju je bilo uključeno 234 bolesnika koji boluju od idiopatske PB, koji su na početku pojave motornih simptoma imali ≥40 godina starosti i koji su bar 2 godine bili na terapiji levodopom. Svaki pacijent je podvrgnut detaljnom neurološkom pregledu, kognitivnoj i bihejvioralnoj proceni. Vršena je genotipizacija za tri polimorfizma u DRD2 genu (rs2283265, rs1076560, rs6277), dva polimorfizma u ANKK1 genu (rs1800497 i rs2734849) i jedan polimorfizam u COMT genu (Val158Met, rs4680). Takođe, određivan je broj ponovaka u 3'UTR regionu DAT gena. Od ukupnog broja ispitanika, diskinezije su bile prisutne kod 51,3%, 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 učestalošću diskinezija. Polimorfizam rs2734849 ANKK1 gena indukovao je vulnerabilnost za pojavu halucinacija kod obolelih ispitanika. Nosioci GG genotipa rs2734849 ANKK1 gena i AA genotipa rs6277 DRD2 gena imali su 2,2, odnosno 2,3 puta veći rizik od pojave psihoze u PB. Pored prethodne izloženosti dopaminergičkim lekovima, motornog statusa, depresije i anksioznosti, kao dobro utvrđenih kliničkih faktora rizika za razvoj psihoze, GG rs2734849 ANKK1 mogao bi, takođe, biti faktor od uticaja, što zahteva potvrdu u budućim longitudinalnim studijama.Polymorphisms in genes involved in dopamine metabolism and transport have been studied concerning 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 selected polymorphisms of the COMT, DRD2, ANKK1, and DAT genes and the occurrence of complications of long-term use of levodopa such as dyskinesias, hallucinations, and psychosis. The study included 234 PD patients who were ≥40 years old at disease onset and on levodopa therapy for at least two years. Each patient underwent a detailed neurological examination and cognitive and behavioral assessment. Genotyping of three polymorphisms in the DRD2 gene (rs2283265, rs1076560, rs6277), two polymorphisms in the ANKK1 gene (rs1800497 and rs2734849), and one polymorphism in the COMT gene (Val158Met, 151 rs4680) was done. Also, a variable number of tandem repeats polymorphism in the 3’UTR region of the DAT gene was determined. Of the participants, dyskinesias were present in 51.3%, hallucinations occurred in 41.9%, and psychosis in 43.2% of patients. Homozygotes for the allele of low COMT activity were associated with a significantly higher incidence of dyskinesias. The rs2734849 ANKK1 gene polymorphism induced vulnerability to hallucinations in PD patients. Carriers of GG genotype rs2734849 ANKK1 gene and AA genotype rs6277 DRD2 gene had a 2.2 and 2.3 times higher risk of developing psychosis in PD, respectively. Besides previous exposure to dopaminergic drugs, impairment of motor status, 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 future longitudinal studies

    Effect of genotype x environment interactions of grapevine hybrids characteristics

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    Research in this paper was performed at two different locations: Radmilovac and Vrsac in Serbia. Four new interspecific hybrids (9846, 9896, 19574 and 20506) which are intended for table consumption were used as a material. Grape yield per unit area, the properties of the bunch (bunch weight, bunch length, bunch width and number of berries in bunch), the properties of berry (berry weight, berry length and berry width), as well as the characteristic of grape quality (sugar content and total acids in the must) were studied in selected hybrids. The highest yield per unit area in the localities Radmilovac and Vr. sac had a hybrid 9896 (14 998 kg/ha; 11 365 kg/ha). Analysis of variance results showed for the bunch weight, bunch width and number of berries in bunch, berry weight and berry length significant differences among the genotypes. Significant differences between investigated localities were determined for the bunch length and all the berry characters. The interaction between genotype and localities showed significant differences for bunch length, berry length and berry width. Since the genotypes in the initial yielding (third year after planting), they are showed satisfactory results in relation to the objectives of selection

    Udruženost polimorfizama gena za katehol-O- metiltransferazu sa terapijskim odgovorom i komplikacijama izazvanim levodopom kod Parkinsonove bolesti: Rezime sadašnjih saznanja

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    Catechol-O-methyltransferase (COMT) is one of the cardinal enzymes in the degradation of catecholamines and levodopa. Genetic variants of the COMT gene may affect COMT enzyme activity. The most examined COMT gene polymorphism is the nonsynonymous single nucleotide polymorphism (SNP) in exon 4 (Val108/158Met; rs4680). This highly functional polymorphism is responsible for fourfold variations in enzyme activity and dopamine catabolism. Recent data suggested that even synonymous SNPs of the COMT gene can lead to changes in enzyme activity. Genetically determined COMT activity can affect an individual's response to levodopa therapy and carries the risk of complications from prolonged levodopa use in Parkinson's disease (PD) patients. Identifying at-risk individuals through genetic susceptibility markers could help to prevent the development of levodopa-induced complications in PD.Katehol-O-metiltransferaza (engl. catechol-O-methyltransferase, COMT) je jedan od glavnih enzima u razgradnji kateholamina i levodope. Genetske varijante COMT gena mogu uticati na aktivnost COMT enzima. Polimorfizam COMT gena koji je najviše proučavan je nesinonimni jednonukleotidni polimorfizam (engl. single nucleotide polymorphism, SNP) u egzonu 4 (Val108/158Met; rs4680). Ovaj visoko funkcionalni polimorfizam odgovoran je za četvorostruke varijacije u aktivnosti enzima i katabolizmu dopamina. Nedavni podaci sugerišu da čak i sinonimni SNP COMT gena mogu da dovedu do promena u aktivnosti enzima. Genetski određene razlike u COMT aktivnosti mogu uticati na odgovor pojedinca na terapiju levodopom i nose rizik od komplikacija dugotrajne primene levodope kod pacijenata sa Parkinsonovom bolešću (PB). Identifikacija osoba u riziku putem markera genetske osetljivosti može pomoći u prevenciji komplikacija izazvanih levodopom kod PB

    Adherence to Medication among Parkinson's Disease Patients Using the Adherence to Refills and Medications Scale

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    Objectives: Adherence to medication is an important factor that can influence Parkinson's disease (PD) control. We aimed to explore patients' adherence to antiparkinsonian medication and determine factors that might affect adherence to medications among PD patients. Methods: A cross-sectional, exploratory survey of PD patients treated with at least one antiparkinsonian drug and with a total score of MoCA (Montreal Cognitive Assessment) ≥26 was conducted. The final sample included 112 PD patients. A patient's adherence was assessed through ARMS (Adherence to Refills and Medications Scale). ARMS scores higher than 12 were assumed lower adherence. In addition, each patient underwent neurological examination, assessment of depression, anxiety, and evaluation of the presence of PD nonmotor symptoms. Results: The mean ARDS value in our cohort was 14.9 ± 2.5. Most PD patients (74.1%) reported lower adherence to their medication. Participants in the lower adherence group were younger at PD onset, had significantly higher UPDRS (Unified PD Rating Scale) scores, as well as UPDRS III and UPDRS IV subscores, HARS (Hamilton Anxiety Rating Scale), and NMSQuest (Non-Motor Symptoms Questionnaire for PD) scores compared to the fully adherent group (p=0.013, p=0.017, p=0.041, p=0.043, and p=0.023, respectively). Among nonmotor PD symptoms, the presence of cardiovascular, apathy/attention-deficit/memory disorders, hallucinations/delusions, and problems regarding changes in weight, diplopia, or sweating were associated with lower adherence. Multivariate regression analysis revealed depression as the strongest independent predictor of lower adherence. Conclusion: Depressed PD patients compared to PD patients without clinical depression had a three times higher risk for lower adherence to pharmacotherapy. Recognition and adequate treatment of depression might result in improved adherence

    Kidney Injury Molecule-1 and Cardiovascular Diseases: From Basic Science to Clinical Practice

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    Despite the recent findings concerning pathogenesis and novel therapeutic strategies, cardiovascular disease (CVD) still stays the leading cause of morbidity and mortality in patients with renal dysfunction, especially acute kidney injury (AKI). Early detection of patients with impaired renal function with cardiovascular risk may help ensure more aggressive treatment and improve clinical outcome. Kidney injury molecule-1 (KIM-1) is a new, promising marker of kidney damage which is currently the focus of countless studies worldwide. Some recent animal and human studies established KIM-1 as an important marker of acute tubular necrosis (ATN) and reliable predictor of development and prognosis of AKI. Food and Drug Administration (FDA) in USA acclaimed KIM-1 as an AKI biomarker for preclinical drug development. Recent data suggest the importance of monitoring of KIM-1 for early diagnosis and clinical course not only in patients with various forms of AKI and other renal diseases but also in patients with cardiorenal syndrome, heart failure, cardiopulmonary bypass, cardiothoracic surgical interventions in the pediatric emergency setting, and so forth. The aim of this review article is to summarize the literature data concerning KIM-1 as a potential novel marker in the early diagnosis and prediction of clinical outcome of certain cardiovascular diseases

    Effect of genotype x environment interactions of grapevine hybrids characteristics

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    Research in this paper was performed at two different locations: Radmilovac and Vršac in Serbia. Four new interspecific hybrids (9846, 9896, 19574 and 20506) which are intended for table consumption were used as a material. Grape yield per unit area, the properties of the bunch (bunch weight, bunch length, bunch width and number of berries in bunch), the properties of berry (berry weight, berry length and berry width), as well as the characteristic of grape quality (sugar content and total acids in the must) were studied in selected hybrids. The highest yield per unit area in the localities Radmilovac and Vršac had a hybrid 9896 (14 998 kg/ha; 11 365 kg/ha). Analysis of variance results showed for the bunch weight, bunch width and number of berries in bunch, berry weight and berry length significant differences among the genotypes. Significant differences between investigated localities were determined for the bunch length and all the berry characters. The interaction between genotype and localities showed significant differences for bunch length, berry length and berry width. Since the genotypes in the initial yielding (third year after planting), they are showed satisfactory results in relation to the objectives of selection

    The correlation between genetic factors and freezing of gait in patients with Parkinson's disease

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    Background: Clinical-related risk factors to freezing of gait (FOG) in Parkinson’s disease (PD) have been iden- tified. Still, the influence of genetic variations on the FOG occurrence has been poorly studied thus far. Aim: We aimed to evaluate the association of six selected polymorphisms of DRD2, ANKK1, and COMT genes with the FOG occurrence and explore the influence of ANNK1/DRD2 haplotypes on the onset of FOG in the group of PD patients. Method: PD patients (n = 234), treated with levodopa for at least two years, were genotyped for the rs4680 in COMT, rs6277, rs1076560, and rs2283265 in DRD2, and rs1800497 and rs2734849 polymorphisms in ANKK1 genes. FOG was evaluated by posing a direct question. In addition, a comprehensive set of clinical scales was applied to all patients. Results: FOG occurred in 132 (56.4%) PD patients in our cohort. Freezers were younger at PD onset, had longer disease duration, used higher levodopa daily doses and dopaminergic agents, and had higher motor and non- motor scales scores than non-freezers. FOG was more frequent among AA rs4680 COMT carriers than AG and GG rs4680 COMT carriers. Independent predictors of FOG were: disease duration of more than ten years, levodopa daily dose higher than 500 mg/day, motor status, and COMT AA genotype. AGGAA and GGAAA haplotypes were revealed as protective and vulnerability factors for FOG occurrence. Conclusion: In addition to previously identified disease- and therapy-related risk factors, our results suggested a possible contribution of dopamine-related genes to the FOG occurrence
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