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Dopamine receptors genes polymorphisms in Parkinson patients with levodopa-induced dyskinesia I. Pozhidaev(1), V.M. Alifirova(2), M.B. Freidin(3), I.A. Zhukova(2), O.Y. Fedorenko(1), D.Z. Osmanova(1), Y.S. Mironova(2), B. Wilffert(4), S.A. Ivanova(1), A.J.M. Loonen(5) (1)Mental Health Research Institute, Molecular Genetics and Biochemistry, Tomsk, Russia (2)Siberian State Medical University, Neurology and Neurosurgery, Tomsk, Russia (3)Research Institute for Medical Genetics, Laboratory of Population Genetics, Tomsk, Russia (4)Groningen Research Institute of Pharmacy, Pharmacotherapy and Clinical Pharmacology, Groningen, The Netherlands (5)Groningen Research Institute of Pharmacy, Pharmacotherapy in Psychiatric Patients, Groningen, The Netherlands Introduction: Long-term levodopa treatment of Parkinson's disease (PD) is frequently complicated by spontaneously occurring involuntary muscle movements called levodopa-induced dyskinesia (LID). LID are a substantial barrier to effective symptomatic management of Parkinson's disease (PD), as up to 45% of L-DOPA users develop LID within 5 years [1]. The exact pathological mechanism of this complication has not yet been elucidated. A lot of studies nowadays which approved complex genetic nature of LID. And these genes are involved not only for oxidative stress, but in drug metabolism too [2–4]. Objective: This study aimed to investigate a possible contribution of polymorphic variants of DRD1, DRD2, DRD2/ANKK1, DRD3, DRD4 genes in the development of LID in PD patients. Methods: 212 patients with Parkinson's disease on levodopa therapy were investigated. Dyskinesia was measured by using Abnormal Involuntary Movement Scale (AIMS). DNA extraction and fluorogenic 5′-exonuclease TaqMan genotyping assays were conducted according to standard protocols and blind to clinical status of the subjects. Genotyping was carried out on 28 SNPs of dopamine receptors (rs4532, rs936461, rs6275, rs1801028, rs4245147, rs134655, rs6277, rs1076560, rs2283265, rs179997, rs6279, rs1076562, rs2734842, rs2734849, rs11721264, rs167770, rs3773678, rs963468, rs7633291, rs2134655, rs9817063, rs324035, rs1800828, rs167771, rs6280, rs1587756, rs3758653, rs11246226) on the MassARRAY® Analyzer 4 (Agena Bioscience™) using the set SEQUENOM Consumables iPLEX Gold 384. SPSS software was used for statistical analysis. Statistical significance of the association testing was established using permutations. P-value |
