TY - JOUR
T1 - Polymorphisms of Catechol-O-Methyl Transferase (COMT) Gene in Vulnerability to Levodopa-Induced Dyskinesia
AU - Ivanova, Svetlana A.
AU - Alifirova, Valentina M.
AU - Pozhidaev, Ivan V.
AU - Freidin, Maxim B.
AU - Zhukova, Irina A.
AU - Osmanova, Diana Z.
AU - Zhukova, Natalia G.
AU - Mironova, Yulia A.
AU - Tiguntsev, Vladimir V.
AU - Fedorenko, Olga Yu
AU - Bokhan, Nikolay A.
AU - Wilffert, Bob
AU - Loonen, Anton J.M.
N1 - Funding Information:
This work resulted from a collaboration between the Mental Health Research Institute in Tomsk and the Groningen Research Institute of Pharmacy (GRIP) of the University of Groningen. The Russian part is carried out within the framework of Tomsk Polytechnic University Competitiveness Enhancement Program. The authors have no conflicts of interest to report.
Publisher Copyright:
© 2019 Journal of Pharmacy and Pharmaceutical Sciences. All rights reserved.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019
Y1 - 2019
N2 - Purpose. Parkinson’s disease (PD), a common neurodegenerative disorder, is usually treated with Levodopa (L-DOPA). The use of this drug, however, is severely limited by the development of side effects of the motor system: Levodopa-induced dyskinesia (LID). The aim of this study is to investigate the association between seven COMT gene single-nucleotide polymorphisms (SNPs) and the development of LID in patients with PD. Methods. 232 Caucasian patients with PD were investigated. 212 patients with PD received Levodopa therapy. Dyskinesia was assessed with the use of the Abnormal Involuntary Movement Scale (AIMS). Genotyping was carried out on seven SNPs of the COMT gene (rs4680, rs6269, rs4633, rs4818, rs769224, rs165774, rs174696) using a real-time PCR method, and blind to the clinical status of the subjects. Results. We found association between four SNPs, rs165774, rs4818, rs4633, rs4680, and LID. When the duration of disease was added as a covariate in regression analysis, however, the results did not reach statistical significance. Only the additive model for rs165774 was found to be close to be statistical significance (OR = 1.627 [0.976–2.741], permutation p = 0.057). Conclusions. The results failed to clearly support a contribution of the studied polymorphisms; this may be related to a dominant relationship with the disease duration confounding the effect on the prevalence of LID.
AB - Purpose. Parkinson’s disease (PD), a common neurodegenerative disorder, is usually treated with Levodopa (L-DOPA). The use of this drug, however, is severely limited by the development of side effects of the motor system: Levodopa-induced dyskinesia (LID). The aim of this study is to investigate the association between seven COMT gene single-nucleotide polymorphisms (SNPs) and the development of LID in patients with PD. Methods. 232 Caucasian patients with PD were investigated. 212 patients with PD received Levodopa therapy. Dyskinesia was assessed with the use of the Abnormal Involuntary Movement Scale (AIMS). Genotyping was carried out on seven SNPs of the COMT gene (rs4680, rs6269, rs4633, rs4818, rs769224, rs165774, rs174696) using a real-time PCR method, and blind to the clinical status of the subjects. Results. We found association between four SNPs, rs165774, rs4818, rs4633, rs4680, and LID. When the duration of disease was added as a covariate in regression analysis, however, the results did not reach statistical significance. Only the additive model for rs165774 was found to be close to be statistical significance (OR = 1.627 [0.976–2.741], permutation p = 0.057). Conclusions. The results failed to clearly support a contribution of the studied polymorphisms; this may be related to a dominant relationship with the disease duration confounding the effect on the prevalence of LID.
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U2 - 10.18433/JPPS29903
DO - 10.18433/JPPS29903
M3 - Article
C2 - 30075828
AN - SCOPUS:85071839363
VL - 21
SP - 340
EP - 346
JO - Journal of Pharmacy and Pharmaceutical Sciences
JF - Journal of Pharmacy and Pharmaceutical Sciences
SN - 1482-1826
IS - 1
ER -