Objective: The aim of this study was to identify novel genetic variants associated with Impulse control disorder (ICD) manifestation in PD patients subject to dopaminergic agonist’s treatment.

Background: ICD accounts as a side-effect of the dopaminergic supplementation therapy in about 14% of the Parkinson’s disease (PD) patients. ICD is defined by the Diagnostic and Statistical Manual of Mental Disorders (DMS-IV) as the failure to resist a temptation, an urge or impulse that may harm oneself or others. Genetic factors are thought to contribute to the manifestation of ICD.

Methods: 60 PD patients with at least 2 years of clinical monitoring were enrolled for this study. 29 of these patients developed ICD (PD-ICD) and 31 constituted the control group (PD-CTL). ICD was assessed using the Questionnaire for Impulsive-compulsive disorders in PD (QUIP) and its rating scale (QUIP-RS). Sociodemographic data and medication type were controlled. Patients were genotyped for 10 genetic variants associated to ICD in general population. Statistical analyses were performed creating contingency tables for each variant and calculating χ2.

Results: Two genetic variants (rs6582078 and rs1352250) of the tryptophan hydroxylase 2 (TPH2) gene presented statistically significant differences in allele and genotype frequencies between the PD-ICD and PD-CTL groups. Moreover, the genotype AA of the rs1352250 was not represented in the PD-ICD group suggesting that it may be protective to the side-effect of the dopaminergic medication. In fact, the G allele and the GG genotype of rs1352250 of TPH2 gene are overrepresented in PD-ICD. Odds ratio estimation demonstrated that G allele carriers have three times increased risk of developing ICD than the no carriers.

Conclusions: Two genetic variants (rs6582078 and rs1352250) of the TPH2 gene were significantly associated to ICD manifestation in PD patients. TPH2 gene encodes the tryptophan hydroxylase enzyme, which participates in the synthesis of serotonin. Our results suggest a prominent role of the serotonin in ICD etiology in PD patients subject to dopaminergic medication.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/impulse-control-disorder-associates-with-tyrosine-hydroxylase-2-gene-variants-in-parkinsons-disease-patients-subject-to-dopaminergic-therapy/