Objective: To investigate an influence of selected polymorphisms in DRD2 and ANKK1 genes on the occurrence of complications of long-term levodopa therapy in Serbian PD patients.
Background: Parkinson`s disease (PD) is conventionally treated with dopamine replacement strategies, which are effective in the early stages of disease. Long-term use of levodopa can cause motor fluctuations, dyskinesias and hallucinations.
Method: The study included 234 PD patients who were treated with levodopa for at least two years. Demographic and clinical data were obtained through the use of a detailed, specially designed questionnaire for this study. Each patient underwent comprehensive neurological examination, assessment of depression and anxiety and cognitive screening. The following instruments were used: Unified Parkinson`s Disease Rating Scale (UPDRS), Hoehn and Yahr PD staging scale (HY), Schwab and England scale, Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS). Dyskinesias were quantified per Abnormal Involuntary Movement Scale (AIMS). For the evaluation of hallucinations we used: Tottori University Halucinattion Rating Scale, and The University of Miami Parkinson’s disease Hallucinations Questionnaire (UM-PDHQ). Genotyping of rs2283265, rs1076560, and rs6277 in DRD2 and rs1800497 and rs2734849 in ANKK1 genes was performed using TaqMan SNP genotyping assays (ThermoFisher Scientific, Foster City, CA) on the ABI Prism 7500 Fast Real-Time PCR System (Applied Biosystems, USA).
Results: From a total of 234 patients, motor fluctuations were present in 75% and dyskinesia in 51% of patients. There were no association between the presence of motor fluctuations, dyskinesias and hallutinations and single nucleotides polymorphisms of DRD2 and ANKK1 genes. Significant lower incidence of motor fluctuations was found in the group of patients with DRD2/ANKK1 AGGAA haplotype, whereas significant higher incidence of motor fluctuations was found among DRD2/ANKK1 GGAAA carriers.
Conclusion: DRD2/ANKK1 GGAAA haplotype is associated with higher frequency of motor fluctuations, while DRD2/ANKK1 AGGAA haplotype has lower frequency of motor fluctuations.
References: 1. Elmyra V. Encarnacion, Robert A. Hauser. Levodopa-Induced Dyskinesias in Parkinson’s disease: Etiology, Impact on Quality of Life, and Treatments. Eur Neurol 2008; 60: 57–66. 2. Ahlskog JE, Muenter MD. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord 2001; 16:448–458. 3. Jankovic J. Motor fluctuations and dyskinesias in Parkinson’s disease: clinical manifestations. Mov Disord. 2005; 20 Suppl 11:S11-6. 4. Fox SH, Lang AE. Levodopa-related motor complications- phenomenology. Mov Disord. 2008; 23 Suppl 3:S509-14. 5. Schrag A, Quinn N. Dyskinesias and motor fluctuations in Parkinson’s disease. A community-based study. Brain 2000; 123(11): 2297–2305. 6. Fénelon G, Mahieux F, Huon R, Ziégler M. Hallucinations in Parkinson’s disease: prevalence, phenomenology and risk factors. Brain 2000; 123:733-745. 7. Kurzawski M, Bialecka M, Drozdzik M, Pharmacogenetic considerations in the treatment of Parkinson´s disease. Neurodegener. Dis. Manag. 2015; 5(1): 27-35 8. Drozdzik M, Bialecka M, Kurzawski M. Pharmacogenetics of Parkinson´s Disease – Through Mechanism of Drug Actions. Current Genomics 2013; 14 (8). 9. Kaiser R, Hofer A, Grapengiesser A et al. L-dopa-induced adverse effects in PD and dopamine transporter gene polymorphism. Neurology 2003; 60 (11): 1750-1755. 10. Kaplan N, Vituri A, Korczyn AD et al. Sequence variants in SLC6A3, DRD2, and BDNF genes and time to levodopa-induced dyskinesias in Parkinson’s disease. J Mol Neurosci. 2014; 53(2):183-188. 11. Contin M, Matinelli P, Mochi M et al. Dopamine Transporter Gene Polymorphism, SPECT Imaging, and Levodopa Response in Patients with Parkinson Disease. Clin Neuropharmacol. 2004; 27 (3): 111-115. 12. Rieck M, Schumacher-Schuh AF, Altmann V et al. DRD2 haplotype is associated with dyskinesia induced by levodopa therapy in Parkonson´s disease patients. Pharmacogenomics. 2012; 13(15): 1701-1710.
To cite this abstract in AMA style:
B. Radojević, N. Dragašević-Mišković, A. Marjanović, A. Milovanović, M. Svetel, I. Petrović, M. Savić, I. Jančić, V. Kostić. The influence of ANNK1/DRD2 haplotypes on the onset of complications of long-term levodopa therapy in Parkinson’s disease [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/the-influence-of-annk1-drd2-haplotypes-on-the-onset-of-complications-of-long-term-levodopa-therapy-in-parkinsons-disease/. Accessed May 17, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-influence-of-annk1-drd2-haplotypes-on-the-onset-of-complications-of-long-term-levodopa-therapy-in-parkinsons-disease/