Session Information
Date: Monday, September 23, 2019
Session Title: Clinical Trials, Pharmacology and Treatment
Session Time: 1:45pm-3:15pm
Location: Agora 3 West, Level 3
Objective: To examine if specific single nucleotide polymorphisms (SNPs) in the genes for dopamine receptors 2 and 3 (DRD2, DRD3) correlate with worse outcomes within specific treatment strategies.
Background: Disease outcomes are heterogeneous in Parkinson’s disease (PD). Pharmacogenetics may be useful in explaining this diversity and informing clinical decisions as to which medications may be most helpful for a specific patient. SNPs in dopamine receptor genes that alter receptor binding offer hypothesis-driven examination of PD outcomes associated with specific medications.
Method: The analysis used data from the NIH Exploratory Trials in PD Long-term Study 1 (NET-PD LS-1). DNA samples (n=540) were genotyped for the rs1800497 and rs6280 SNPs. The primary outcomes were the Unified PD Rating Scale (UPDRS), its motor component (UPDRS-III) and the 39-item Parkinson Disease Questionnaire (PDQ-39) as assessed at time 0 in the On state for each subject. Groups were created by dividing by presence of risk allele and then one of two treatment regimens: levodopa monotherapy or no levodopa (with mixed regimens excluded).
Results: Subjects with the rs1800497 A/A genotype (~6%) had significantly worse mean UPDRS scores with levodopa monotherapy than without levodopa (33.7 vs 22.1, p=0.01) and with a trend by UDPRS-III; however, G/G and G/A genotypes had no significant differences between treatment strategies. Similarly, subjects with the rs6280 C/C genotype (~11%) had significantly worse mean UPDRS scores with levodopa monotherapy (35.0 vs 26.4, p=0.04) with a trend by UPDRS-III, but no differences between treatment strategies detected within T/T or T/C genotype groups.
Conclusion: A levodopa monotherapy treatment strategy is associated with worse disease outcomes in the setting of specific dopamine receptor variants. If validated, risk alleles may be precision medicine factors to consider for symptomatic treatment decisions for PD patients. This research was supported by grants from the United States National Institute of Neurological Disorders and Stroke (NINDS, #NS095656) and the Saint Mary’s Foundation (Grand Rapids, MI, USA).
To cite this abstract in AMA style:
D. Fischer, P. Auinger, J. Goudreau, A. Cole-Strauss, K. Kieburtz, J. Elm, M. Hacker, P. Charles, J. Lipton, B. Pickut, C. Sortwell. Dopamine receptor variants alter outcomes with levodopa in early-stage Parkinson’s disease [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/dopamine-receptor-variants-alter-outcomes-with-levodopa-in-early-stage-parkinsons-disease/. Accessed June 15, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/dopamine-receptor-variants-alter-outcomes-with-levodopa-in-early-stage-parkinsons-disease/