Objective: We aimed to study the association between glutamatergic system gene polymorphisms (SLC1A2 – gene, coding excitatory acids transporter, and GRIN2A gene, coding a subunit of NMDA receptor) and development of Levodopa-induced dyskinesias (LID) in Parkinson’s disease (PD).

Background: LID are the most common complication of long-term dopaminergic therapy in PD. Pathophysiologic mechanisms behind LID are not entirely understood despite growing body of research. Even considering all known predisposing factors, it is still unclear why some patients don’t experience LID even after a decade of levodopa therapy while others develop this complication early in the course of the disease, suggesting the critical role of genetic factors. The glutamate hypothesis of LID pathogenesis received a lot of attention over time as the only approved medication for management of this complication presumably acts on glutamate receptors.

Methods: The study group included 187 patients with PD that were divided into two subgroups: patients with LID (n=40) and without LID (n=147). Dyskinesia was measured by using Abnormal Involuntary Movement Scale. We performed genotyping of two single-nucleotide polymorphisms (SNP) of GRIN2A gene (rs1969060, rs2650427) and one SNP of SLC1A2 gene (rs4354668). DNA extraction and fluorogenic 5′-exonuclease TaqMan genotyping assays were conducted according to standard protocols. Statistical analysis was performed using IBM SPSS 23.

Results: The distribution of genotypes of studied genes corresponded to the Hardy-Weinberg equilibrium. We found that rs1969060 polymorphism of GRIN2A in patients with LID was characterized by increased prevalence of GG genotype (11,1%) and decreased prevalence of AG genotype (2,8%) when compared to distribution in a group of patients without LID: 3,7% and 14% respectively (χ2=6,12; р=0,05). The group with LID also showed the decreased prevalence of TT genotype (8,6%) and increased prevalence of CT (68,6%) of rs2650427 polymorphism GRIN2A compared to patients without LID: 20% and 46.2% respectively (χ2=5,83; р=0,05). The odds ratio for rs2650427 polymorphism of GRIN2A gene was high for CT genotype (OR=2,55; 95% CI=1,15-5,62) which may point to its LID-predisposing effect. Analysis of frequency distribution between groups based on rs4354668 polymorphism of SLC1A2 gene didn’t identify significant differences.

Conclusions: The obtained results show that the polymorphic variants of the glutamatergic system genes are an essential factor in the pathogenesis of LID. Our findings confirm that furthering research of PD genetics can contribute to both clinical decision-making and fundamental understanding of disease mechanisms.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/polymorphisms-of-glutamatergic-system-genes-are-associated-with-levodopa-induced-dyskinesia-in-parkinsons-disease/