Association of DRD3 and GRIN2B with Impulse Control and Related Behaviors in Parkinson’s Disease Jee-Young Lee, MD, 1 Eun Kyung Lee, RN, 2 Sung Sup Park, MD, PhD, 2,3 Ji-Yeon Lim, BS, 2 Hee Jin Kim, MD, 2,4 Ji Sun Kim, MD, 5 and Beom S Jeon, MD, PhD 2,4,6 * 1 Department of Neurology, Inje University Ilsan Paik Hospital, Goyang, Korea 2 Clinical Research Institute and Movement Disorders Center, Seoul National University Hospital, Seoul, Korea 3 Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea 4 Department of Neurology, Seoul National University Hospital, Seoul, Korea 5 Department of Neurology, Seoul National University Bundang Hospital, Seongnam, Korea 6 Neuroscience Research Institute, College of Medicine, Seoul National University, Seoul, Korea Abstract: We aimed to assess whether allelic variants of do- pamine 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 trans- porter 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 asso- ciated with the risk of developing ICRB. However, the AA ge- notype 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] 5 2.21, P 5 0.0094; and 2.14, P 5 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 5 0.0087). Variants of DRD3 p.S9G and GRIN2B c.366C>G may be associated with the appear- ance of ICRB in PD. Ó 2009 Movement Disorder Society Key words: impulse control and related behavior; Parkin- son’s disease; genetic association; dopamine receptor; gluta- mate NMDA receptor type 2B; serotonin transporter INTRODUCTION Impulse control and related behaviors (ICRB) has been recently recognized as a long-term complication of dopamine replacement therapy (DRT) in patients with Parkinson’s disease (PD). 1 The proposed category of ICRB in PD includes addictive behaviors, such as problem/pathological gambling, compulsive shopping, hypersexuality, compulsive eating, and punding, which is an aimless repetitive stereotyped performance of complex tasks. 2 The lifetime prevalence of ICRB in PD is not known, but several hospital-based surveys have sug- gested that they are not rare (2–14%). 3–5 Because patients with ICRB are likely to experience serious social problems, identification of predisposing factors is an important issue in the management of PD. 1,2 The development of ICRB is closely related with dopamine agonist use and dose of dopaminergic medications, 3–6 whereas in some patients novelty-seeking trait, impul- sivity, and family history of alcohol use disorder are predisposing factors of ICRB. 7,8 Thus, underlying Potential conflict of interest: nothing to report. Additional Supporting Information may be found in the online ver- sion of this article. *Correspondence to: Beom S. Jeon, Department of Neurology, Clinical Research Institute and Movement Disorders Center, Seoul National University Hospital, Seoul 110-744, Korea. E-mail: brain@snu.ac.kr Received 27 February 2009; Revised 22 April 2009; Accepted 19 May 2009 Published online 26 June 2009 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.22678 1803 Movement Disorders Vol. 24, No. 12, 2009, pp. 1803–1810 Ó 2009 Movement Disorder Society