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), in Parkinson’s disease (PD) patients.

Background: LID is the most common and most disabling side effect of long-term levodopa therapy. Their development depends on the individual characteristics of the disease and the pharmacological factors, while more data indicate abnormal neuroplasticity of the monoamine metabolism system.

Method: Our prospective 10 years of the clinical study is included 320 sporadic PD patients from Russia. The analysis of 18 SNPs of dopamine and serotonin receptors, serotonin transporter, monoamine oxidase B, catechol-O-methyltransferase, tryptophan hydroxylase and tyrosine hydroxylase genes is performed. Afterward 10 years dyskinesia are estimated using of MDS-UPDRS scale (parts IV and IVA). Linear regression and one-way ANOVA test are used. A P-value<0,05 is considered statistically significant.

Results: Thus, the presence of LID is evaluated in 80 PD patients from the original cohort, and dyskinesia are reported in 25 (68,75%) patients. It is revealed that  statistically DRD2 rs6275, TPH1 rs1800532, LRRK2 rs1491942 and DRD3 rs6280 polymorphisms are significantly associated with LID.
Patients homozygous of the rs6275*G allele had higher values of the part IV UPDRS scale compared to heterozygous (p=0,024) according to the results of linear regression analysis.
Carriers of the rs1800532*G/T heterozygous had lower values of the part IV MDS- UPDRS scale compared to carriers of the homozygous *G/G and *T/T carriers (p=0,038).
It is found that patients with LID have a higher incidence of the rs6280*C/C of the DRD3 gene (p=0,022; OR=0,05) compared to the without dyskinesia. Two loci found a borderline association: patients with LID have a higher incidences of the rs6311*A of the HTR2A gene (p=0,059; OR=2,23) and of the rs1799836*A allele of the MAO-B gene (p=0,050; OR=2,19) compared to the patients who didn’t have dyskinesia.

Conclusion: Thereby, the determined genetic risk factors in development of LID are revealed. It is required to conduct the investigations on the larger sampling. This pilot study will be continuing.
The work was supported by RFBR grant #19-015-00331.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-study-of-the-role-of-genetic-risk-factors-in-levodopa-induced-dyskinesia-development-in-russian-patients-with-parkinsons-disease-a-pilot-study/