Suggestive association between OPRM1 and impulse control disorders in Parkinson's disease.
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Cormier-Dequaire Florence, Bekadar Samir, Anheim Mathieu, Lebbah Said, Pelissolo Antoine, Krack Paul, Lacomblez Lucette, Lhommée Eugénie, Castrioto Anna, Azulay Jean-Philippe, Defebvre Luc, Kreisler Alexandre, Durif Franck, Marques-Raquel Ana, Brefel-Courbon Christine, Grabli David, Roze Emmanuel, Llorca Pierre-Michel, Ory-Magne Fabienne, Benatru Isabelle, Ansquer Solene, Maltête David, Tir Melissa, Krystkowiak Pierre, Tranchant Christine, Lagha-Boukbiza Ouhaid, Lebrun-Vignes Bénédicte, Mangone Graziella, Vidailhet Marie, Charbonnier-Beaupel Fanny, Rascol Olivier, Lesage Suzanne, Brice Alexis, Tezenas du Montcel Sophie, Corvol Jean-Christophe, BADGE-PD study group
Аннотация
METHODS: We performed a multicenter case-control study in PD patients with (cases) or without impulse control disorders and related behaviors despite significant dopamine agonist exposure of >300 mg levodopa-equivalent daily dose during 12 months (controls). Behavioral disorders were assessed using the Ardouin scale. We investigated 50 variants in 24 candidate genes by a multivariate logistic regression analysis adjusted for sex and age at PD onset.
RESULTS: The analysis was performed on 172 cases and 132 controls. Cases were younger (60 ± 8 vs 63 ± 8 years; P < 0.001) and had a higher family history of pathological gambling (12% vs 5%, P = 0.03). No variant was significantly associated with impulse control disorders or related behaviors after correction for multiple testing, although the 2 top variants were close to significant (OPRM1 rs179991, OR, 0.49; 95%CI, 0.32-0.76; P = 0.0013; Bonferroni adjusted P = 0.065; DAT1 40-base pair variable number tandem repeat, OR, 1.82; 95%CI, 1.24-2.68; P = 0.0021; Bonferroni adjusted P = 0.105).
CONCLUSIONS: Our results are suggestive of a novel association of the opioid receptor gene OPRM1 with impulse control disorders and related behaviors in PD and confirm a previous association with DAT1. Although replication in independent studies is needed, our results bring potential new insights to the understanding of molecular mechanisms of impulse control disorders. © 2018 International Parkinson and Movement Disorder Society.