Objective: The aim of this study was to investigate the association between two DRD3 gene single-nucleotide polymorphisms (SNPs) and the development of LID in patients with PD.

Background: Parkinson’s disease (PD), a common neurodegenerative disorder. Levodopa-induced dyskinesia (LID) is common side effect of Levodopa (L-DOPA) treatment. LID developed in a third of patients during the first two years of treatment.

Method: 140 Caucasian patients with PD were assessed: 90 (65%) are women and 50 (35%) are men. The age of patients ranged from 44 to 83 years, the average age was 71.4±7.6 years. The age of onset of the disease averaged 59.3±8.5 years. The duration of the disease at the time of the survey was 12.2±4.8 years. 72 patients (51.4%) received levodopa medications. Evaluation of LID was performed using the Abnormal Involuntary Movement Scale (AIMS). Genotyping was carried out on two SNPs of the DRD3 gene (rs9817063 and rs167770)  using a real-time PCR method.

Results: The study found that the frequency of occurrence of the AG genotype (rs9817063) in patients with LID is 52.5%. These patients have low AIMS values. The frequency of AA genotype (rs9817063) in patients with LID is 25%, which is significantly higher than in other groups. It was also found that patients with LID and the AA genotype (rs9817063) have the highest overall AIMS scores and more severe dyskinesias in the limbs and torso. The AG (rs167770) genotype in patients with LID is found in 37% of cases. In this group, patients have lower severity of pathological involuntary movements in the limbs and torso, as well as lower overall values on the AIMS scale than patients with the AA genotype (rs167770). The frequency of occurrence of this genotype was 61%. Patients with LID and the AA genotype (rs167770) had higher overall AIMS values and more severe dyskinesia in the limbs and trunk than in patients in the other studied groups.

Conclusion: Thus, it was established that with rs9817063 and rs167770 polymorphisms of the dopamine receptor gene DRD3 in patients with PD and AA genotype, the likelihood of LID is higher than in patients with other genotypes. Patients with PD and AA genotype without dyskinesias are at risk, as it is impossible to deny the possibility of dyskinesias in these patients in the future.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/levodopa-induced-dyskinesia-in-patients-with-parkinsons-disease-and-polymorphisms-gene-drd3-dopamine-receptor/