Objective: To test if the allelic variants of dopamine (DRD3), glutamate (GRIN2B) and serotonin (HTR2A) receptors are risk factors for ipulse control disorders (ICD) in Indian Parkinson’s disease patients.

Background: Genetic vulnerability is suspected to underlie the individual risk for ICD n Parkinson’s disease (PD).

Methods: In this prospective, case-control study we included PD patients (70 with ICD, 100 without ICD, categorized after direct psychiatric interview of patient and caregiver) and 285 healthy controls. Single nucleotide polymorphism (SNP) variants of DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) were genotyped.

Results: Multivariate regression analysis revealed that DRD3 p.Ser9Gly (rs6280) heterozygous variant CT (OR= 2.22, p=0.041), higher levodopa equivalent doses (LED) of drugs (for 100mg LED (OR= 1.14, p=0.041), current dopamine agonist use (OR=2.16, 95%, p= 0.042) and age of onset of motor symptoms under 50 years (OR 2.09, p =0.035) were independent risk factors for ICD.

Conclusions: Indian PD patients who are carriers of DRD3 p.Ser9Gly (rs6280) CT genotype are at higher risk to develop ICD and this genetic association with ICD is not reported so far. We propose that in carriers of this genotype, enhanced D3 receptor affinity due to gain-of-function conferred by the glycine residue could accentuate alterations in tonic and phasic release of dopamine in the ventral striatum during preferential D3 agonist use. This could affect reward-risk assessment in the mesolimbic system and generate impulsive behaviour.

Submitted for 19th congress but withdrawn due to inability to travel.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dopamine-d3-receptor-ser9gly-variant-is-a-risk-factor-for-impulse-control-disorders-in-parkinsons-disease/