Category: Parkinson's Disease: Genetics
Objective: We examined the influence of single nucleotide polymorphisms (SNPs) in specific genes on levodopa-induced dyskinesia development in Parkinson’s disease patients
Background: Levodopa-induced dyskinesia (LID) is commonly seen in Parkinson’s disease patients treated with levodopa for a long time.
Method: Our prospective 10 years clinical study included 674 sporadic PD patients from Russia. Among them there are 300 PD patients completing dyskinesia evaluation using of MDS-UPDRS scale (parts IVA) afterward 10 years. PD patients were divided into PD with LID (PD-LID) and PD without LID (PD-NORM). The analysis of 22 SNPs of serotonin transporters 5-HTT (5-HTTLPR and Stin2) and receptors HTR1B, HTR2A, HTR2C (rs6296; rs6311; rs6318), catechol-o-methyltransferase COMT (rs4680), tryptophan hydroxylase TPH (rs1800532), NMDA receptor GRIN2A (rs8057394 and rs7192557), adenosine receptor ADORA2A (rs2298383 and rs3761422), brain‐derived neurotrophic factor BDNF (rs6265), protein HOMER1 (rs4704559) genes was performed. The SPSS software is used for statistical analysis. APSampler algorithm was used for search genetic combinations. Linear regression analysis and one-way ANOVA test are used. P-value <0,05 is considered statistically significant.
Results: The presence of all motor levodopa-induced complications was assessed in 300 PD patients (106 male, 35.33%), and dyskinesias were identified in 151 (50.33%). There were no statistical differences in rs4680 genotype or allele frequencies were observed between patients with LID and patients without LID patients.
Conclusion: Few studies examining associations between rs4680 and LID showed inconsistent results: only one study considering the impact potential confounders (in particular, the duration and dosage of dopaminergic therapy) confirmed the presence of this relation. This study suggested that rs4680 of COMT gene can be a genetic risk factor for levodopa-induced dyskinesia development. This study will be continued on expanded samples.
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, O. Kachemaeva, A. Baitimerov, R. Galimova, R. Magzhanov. COMT polymorphism as a genetic factor in levodopa-induced dyskinesia development in Russian patients with Parkinson’s disease [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/comt-polymorphism-as-a-genetic-factor-in-levodopa-induced-dyskinesia-development-in-russian-patients-with-parkinsons-disease/. Accessed June 15, 2025.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/comt-polymorphism-as-a-genetic-factor-in-levodopa-induced-dyskinesia-development-in-russian-patients-with-parkinsons-disease/