RESUMEN
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 χ(2) test. RESULTS: Genotyping was performed for variants of the DRD2 Taq1A (rs1800497), COMT Val(158)Met (rs4680), DAT1 (3' UTR 40bp 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.
Asunto(s)
Catecol O-Metiltransferasa/genética , Trastornos Disruptivos, del Control de Impulso y de la Conducta/etiología , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/genética , Polimorfismo Genético , Receptores de Dopamina D2/genética , Anciano , Estudios de Cohortes , Trastornos de Alimentación y de la Ingestión de Alimentos/etiología , Femenino , Juego de Azar/etiología , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite/genéticaRESUMEN
Recent evidence suggests that trace amines such as tyramine and octopamine, alternative products of tyrosine metabolism (an aminoacid parent of dopamine and noradrenaline), play a role in the homeostasis of the extrapyramidal system. However, the relevance of these trace amines in the pathogenesis of Parkinson's disease is still largely unknown. Here, we assessed the plasma levels of octopamine and noradrenaline in three sub-groups of PD patients, namely de novo, non-fluctuating and fluctuating patients, versus age-matched control subjects. We show that octopamine is detectable in plasma of all subjects, the mean levels of which are significantly lower in PD patients, including de novo patients, when compared to controls (p<0.001). Unlike this, no changes in plasmatic noradrenaline levels were found in the de novo patients, but only in plasma of fluctuating and non-fluctuating PD patients. These findings raise the possibility that Parkinson's disease is firstly characterized by abnormalities of tyrosine decarboxylase, rather than tyrosine hydroxylase, enzyme activity. Given the role of this enzyme in the production of trace amines, circulating octopamine levels may hold promise as a biomarker of early Parkinson's disease.