Objective: To investigate the association between candidate genes and impulse control disorders (ICD) in patients with Parkinson’s disease.

Background: ICD are frequently associated with dopaminergic therapy in Parkinson’s disease (PD). Genetic studies have suggested a high heritability of ICD in the general population and in PD. 

Methods: We performed a multicenter genetic case-control study in PD patients with ICD or without ICD related to dopamine therapy, receiving a treatment with dopamine agonist for at least 12 months at 300 mg equivalent daily dose. Cases and controls were matched for age, sex, and disease duration. Patients were assessed during a face-to-face interview with the French Behavioral Scale for PD. Presence of ICD was defined as 1 severe (score > 3) or 2 moderate (score > 2) hyperdopaminergic behaviors. Patients were considered without ICD if hyperdopaminergic behaviors were absent. The study was powered to investigate 50 polymorphisms preselected from 24 candidate genes. We performed a multivariate logistic regression analysis with a discovery step in 33% random samples, a replication step in the 66% leftover samples, and a pooled analysis, taking into account multiple testing.

Results: We enrolled 176 PD patients with ICD and 136 PD patients without ICD. Patients with ICD were younger (59 +/- 8 versus 62 +/- 7, p<0.001), and had a higher family history of pathological gambling (11% versus 4%, p = 0.04). ICD were pathological gambling (31%), pathological shopping (38%), binge eating (58%), and hypersexuality (43%). At the discovery step, polymorphisms in the DRD2, GRIN2B, OPRM1, CA12, and C8B genes were significantly associated with ICD. The μ opioid receptor gene (OPRM1) polymorphism rs1799971 was replicated in the leftover sample (OR [CI95%] = 0.48 [0.27 – 0.84], p=0.01), and remained significant in the pooled analysis (OR = 0.45 [0.29 – 0.69], p=0.0003).

Conclusions: In PD patients treated with dopamine agonists, we found a significant association between ICD and rs1799971, a functional variant of OPRM1 previously associated with a decreased sensitivity to morphine, and drug or alcohol addiction. Our results suggest an involvement of the opioid system in the behavioral response to dopaminergic therapy in PD.

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/genetics-of-impulse-control-disorders-in-parkinsons-disease-a-case-control-study/