Category: Parkinson's Disease: Genetics
Objective: This study is aimed to explore the relationship between the single nucleotide polymorphisms (SNPs) in dopamine metabolism genes and development of motor side effects of levodopa therapy, such as levodopa-induced dyskinesia (LID) and motor fluctuations (MF) in Russian patients with Parkinson’s disease (PD).
Background: Long-term levodopa treatment for PD patients is frequently associated with the development of motor levodopa-induced complications. The difference in their development supposes a complex pathomechanism including also genetic factors.
Method: Our clinical study was included 674 sporadic PD patients from Russia. The analysis of 7 SNPs of transporters dopamine SLC6A3 (rs393795) and dopamine receptors DRD1-DRD4 (rs4532, rs1800497, rs6275, rs6280, VNTR 48bp and VNTR 120bp) genes was performed. Motor levodopa-induced complications were estimated using of MDS-UPDRS scale, parts IV (A, dyskinesia, and B, motor fluctuations). 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 300 PD patients (106 male, 35.33%). Motor fluctuations occurred in 225 patients (75.0%) and dyskinesias were identified in 151 (50.33%).
Patients homozygous for the rs393795*C/C and rs393795*A/A of SLC6A3 gene had lower values of the part IV (A) MDS-UPDRS scale compared with heterozygous of *С/A (p=0.037; OR=0.61; 95%CI 0.38–0.97).
There was significant association between DRD3 gene and motor complications severity by using MDS-UPDRS IV (A) under additive genetic model (allele rs6280*C, p=0.049; β=-0.426, 95%CI -0.85 – -0.002) and using whole MDS-UPDRS IV scale under additive genetic model (allele rs6280*C, p=0.009; β=-1.21, 95%CI -2.11 – -0.3).
Conclusion: The dopamine transporter and receptors regulate dopaminergic transmission, and genes expression disturbances can lead to motor complications development.
The work was supported by RFBR grant #19-015-00331
To cite this abstract in AMA style:
G. Akhmadeeva, I. Khidiyatova, I. Gilyazova, S. Umutbaev, A. Baitimerov, O. Kachemaeva, R. Galimova, R. Magzhanov. The study of genetic factors in motor levodopa-induced complications development in Russian patients with Parkinson’s disease [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/the-study-of-genetic-factors-in-motor-levodopa-induced-complications-development-in-russian-patients-with-parkinsons-disease-2/. Accessed June 15, 2025.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-study-of-genetic-factors-in-motor-levodopa-induced-complications-development-in-russian-patients-with-parkinsons-disease-2/