Association of <i>DRD3</i> and <i>GRIN2B</i> with impulse control and related behaviors in Parkinson's disease

Abstract

We aimed to assess whether allelic variants of dopamine receptor, glutamate receptor, and serotonin transporter genes are associated with the appearance of impulse control and related behaviors (ICRB) in Parkinson's disease (PD) with dopamine replacement therapy (DRT). We surveyed ICRB in consecutive Korean patients with PD who were treated with stable DRT using modified Minnesota Impulsive Disorders Interview over a period of 4 months. In the 404 patients who completed the interview and the 559 Korean healthy normal controls, genotyping was performed for variants of the DRD3 p.S9G, DRD2 Taq1A, GRIN2B c.366C>G, c.2664C>T and c.-200T>G, and the promoter region of the serotonin transporter gene (5-HTTLPR). Behavioral abnormalities suggestive of ICRB including compulsive buying, gambling, sexual behavior and eating, and punding, were present in 14.4% of the patients. Variants of DRD2 and 5-HTTLPR were not associated with the risk of developing ICRB. However, the AA genotype of DRD3 p.S9G and the CC genotype of GRIN2B c.366C>G were more frequent in patients with ICRB than in nonaffected patients (odds ratio [OR] = 2.21, P = 0.0094; and 2.14, P = 0.0087, after adjusting for age and sex). After controlling for clinical variables in the multivariate analysis, carriage of either AA genotype of DRD3 or CC genotype of GRIN2B was identified as an independent risk factor for ICRB (adjusted OR: 2.57, P = 0.0087). Variants of DRD3 p.S9G and GRIN2B c.366C>G may be associated with the appearance of ICRB in PD.