Category: Parkinson's Disease: Genetics
Objective: The aim of our study is to search for genetic risk factors for the development of motor side effects of dopaminergic therapy, such as levodopa-induced dyskinesia (LID) and motor fluctuations (MF) in Parkinson’s disease (PD) patients.
Background: Long-term levodopa treatment for PD patients is frequently associated with the development of motor levodopa-induced complications such as motor fluctuations (end-of-dose wearing-off) and dyskinesias. The difference in their development supposes a complex pathomechanism including also genetic factors.
Method: Our clinical study was included 631 sporadic PD patients from Russia. The analysis of 7 SNPs of transporters dopamine SLC6A3 gene (rs393795), and genes of other monoamine metabolism system and abnormal neuroplasticity – NMDA receptor GRIN2A (rs8057394 and rs7192557), adenosine receptor ADORA2A (rs2298383 and rs3761422), brain‐derived neurotrophic factor BDNF (rs6265), protein HOMER1 (rs4704559) genes was performed. Dyskinesia was estimated using of MDS-UPDRS scale (parts IV). The SPSS software was used for statistical analysis. Linear regression and one-way analysis of variance (ANOVA) were used. A P-value<0,05 was considered statistically significant.
Results: Thus, the presence of all motor levodopa-induced complications was assessed in 203 PD patients. Motor fluctuations occurred in 168 (82.76%) patients (107 female, 61 male) and dyskinesias were identified in 105 (51.72%).
Our one-way analysis of variance revealed statistically significant results on the association of the polymorphic marker ADORA2A rs3761422 with the severity of motor fluctuations. Thus, patients homozygous of the rs3761422*C allele had higher values of the part IV (B) UPDRS scale compared to homozygous of the rs3761422*T allele (F=3.831; p=0.024).
Conclusion: The ADORA2A gene is expressed in the striatum and negatively affects the activity of the dopamine D2 receptor (DRD2), which is known to be the main binding site for dopamine in the nitrostriatum in patients with PD. This study identifies possible genetic risk factors for the development of the motor levodopa-induced complications. It will be continuing.
The work was supported by RFBR grant #19-015-00331
To cite this abstract in AMA style:
G. Akhmadeeva, I. Khidiyatova, I. Gilyazova, G. Tayupova, S. Umutbaev, A. Baitimerov, R. Magzhanov. The study of genetic factors in motor levodopa-induced complications development in Russian patients with Parkinson’s disease [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/the-study-of-genetic-factors-in-motor-levodopa-induced-complications-development-in-russian-patients-with-parkinsons-disease/. Accessed May 19, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-study-of-genetic-factors-in-motor-levodopa-induced-complications-development-in-russian-patients-with-parkinsons-disease/