Short communication Role of genetic polymorphisms of the dopaminergic system in Parkinson’s disease patients with impulse control disorders Annamaria Vallelunga a, * , Raffaella Flaibani a , Patrizia Formento-Dojot b , Roberta Biundo b , Silvia Facchini b , Angelo Antonini b a Molecular Neurobiology Laboratory, IRCCS San Camillo, via Alberoni 70, 35126 Venice Lido, Italy b Department for Parkinson’s disease, IRCCS San Camillo, via Alberoni 70, 35126 Venice Lido, Italy article info Article history: Received 28 June 2011 Received in revised form 27 October 2011 Accepted 31 October 2011 Keywords: Impulse control disorder Mechanisms Genetic DRD2 Taq1A COMT DAT1 Parkinson disease Dopamine agonist Levodopa Pramipexole Ropinirole Dopaminergic therapy abstract Background: The mechanisms underlying the development of impulse control disorders (ICDs) like compulsive gambling, buying, sexual, and eating behaviors in Parkinson’s disease (PD) are debated. We assessed whether allelic variants of dopamine D2 receptors (DRD2), catechol-O-methyltransferase (COMT) and dopamine transporter (DAT) were associated with the development of ICDs in PD. Method: We enrolled 89 idiopathic PD patients (48 without ICDs and 41 with ICDs). All patients were screened with the Minnesota Impulsive Disorders Interview (MIDI) and fulfilled DSM-IV criteria for the ICD positive cohort. Differences in the frequency of the genotypes between ICDs and non-ICDs groups were assessed using the c 2 test. Results: Genotyping was performed for variants of the DRD2 Taq1A (rs1800497), COMT Val 158 Met (rs4680), DAT1 (3 0 UTR 40 bp VNTR). Variants of DRD2 Taq1A, COMT and DAT1 were not associated with the risk of developing ICDs. Conclusion: In our study, there were no differences in the frequency of variant of DRD2 Taq1A, COMT and DAT1 between the two groups. Polymorphisms of dopaminergic genes do not play a relevant role in the development of ICD in PD suggesting that ICD originate from inability to filter inappropriate behaviors triggered by dopaminergic therapy. Ó 2011 Published by Elsevier Ltd. 1. Background The mechanisms underlying the development of impulse control disorders (ICDs) like compulsive gambling, buying, sexual, and eating behaviors in Parkinson’s disease (PD) are debated. ICDs commonly develop after the initiation of dopaminergic therapy but predisposing behavioral traits have been recently reported also in newly diagnosed “de novo” patients [1]. Risk factors are use of dopamine agonists as well as novelty-seeking personality, impul- sivity, and family history of alcohol use disorders [2]. Genetic polymorphisms of Dopamine D2 receptors (DRD2), dopamine transporter (DAT) and Catechol-O-methyltransferase (COMT) may contribute to the development of ICDs in PD through abnormal modulation of dopaminergic transmission and signaling in the mesocorticolimbic dopaminergic system [3]. DRD2 are most commonly found in GABAergic interneurons of the prefrontal cortex (PFC) and striatal regions. The human DRD2 gene contains several polymorphic sites and Taq1A locus located in the 3 0 untranslated region of the gene. The DRD2 Taq1A restriction fragment length polymorphism (RFLP) results in an amino acid substitution (Glu 713 Lys) in a serine/threonine kinase which may affect substrate binding to the DRD2 receptor and it is associated with decreased striatal D2 receptors [4]. There is evidence for an association between DRD2 Taq1A polymorphism and alcohol dependence especially in impulsive form of alcoholism [12]. DRD2 Taq1A polymorphism was also associated with substance misuse dependence in both Caucasian and non-Caucasians. Furthermore, the DRD2 Taq1A polymorphism was related to pathological gambling suggesting a role in susceptibility to a range of malad- aptive behaviors [13]. COMT is the major mammalian enzyme involved in the meta- bolic degradation of released dopamine (DA) and accounts for more than 60% of the metabolic degradation of DA in the prefrontal cortex. The Val 158 Met single nucleotide polymorphism is a common valine- to-methionine substitution, leading to a three to fourfold decrease * Corresponding author. Tel.: þ39 (0)412207246. E-mail address: biologia.molecolare@ospedalesancamillo.net (A. Vallelunga). Contents lists available at SciVerse ScienceDirect Parkinsonism and Related Disorders journal homepage: www.elsevier.com/locate/parkreldis 1353-8020/$ e see front matter Ó 2011 Published by Elsevier Ltd. doi:10.1016/j.parkreldis.2011.10.019 Parkinsonism and Related Disorders 18 (2012) 397e399