Dissimilar mechanistic background of peripheral and orofacial hyperkinesia in patients with Parkinson’s disease and levodopa-induced dyskinesia

Introduction: long-term levodopa treatment of parkinson’s disease (pd) is frequently complicated by spontaneously occurring involuntary muscle movements called dyskinesia. the exact pathological mechanism of this complication has not yet been elucidated. we have previously demonstrated that in pd patients the vulnerability to develop peripheral but not orofacial dyskinesia is associated with the presence of two variants of the grin2a gene. moreover, we have shown that in tardive dyskinesia (td) orofacial dyskinesia is associated with other polymorphisms as compared with peripheral dyskinesia. in the present study we investigate whether the peripheral versus orofacial nature of levodopa-induced dyskinesia (lid) in pd can be explained by considering polymorphisms for dopaminergic and serotonergic receptors. materials and methods: 101 russian patients with pd (38m/63f) were examined. genotyping was carried out on 19 snps for 3 neurotransmitter genes: 10 snps for drd3 gene (rs11721264, rs167770, rs3773678, rs963468, rs7633291, rs2134655, rs9817063, rs324035, rs1800828, rs167771), 1 snp for drd4 gene (rs3758653), and 8 snps for htr2c gene (rs6318, rs5946189, rs569959, rs17326429, rs4911871, rs3813929, rs1801412, rs12858300). results: genotyping patients with pd and lid revealed that only rs3773678 (drd3, dominant, p = 0.042) was associated with orofacial dyskinesia. conclusion: the findings of the current study are not related to lid in pd itself, but to other forms of orofacial dyskinesia in this patient group. abbreviations: pd – parkinson’s disease; td – tardive dyskinesia; lid – levodopainduced dyskinesia; msn – medium spiny neuron; nmda – n-methyl-d-aspartate; hd – huntington’s disease; snp – single nucleotide polymorphism