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

Svetlana A. Ivanova, Olga Yu Fedorenko, Maxim B. Freidin, Valentina M. Alifirova, Natalia G. Zhukova, Irina A. Zhukova, Asmar F Y Al Hadithy, Jacobus R B J Brouwers, Nikolay A. Bokhan, Bob Wilffert, Anton J M Loonen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)216-221
Number of pages6
JournalPhysiology and Pharmacology
Volume19
Issue number4
Publication statusPublished - 1 Dec 2015

Fingerprint

Hyperkinesis
Dyskinesias
Levodopa
Parkinson Disease
Disease
Single Nucleotide Polymorphism
Genes
Parkinson's Disease
vulnerability
Gene
Smooth Muscle
Neurotransmitter Agents

Keywords

  • Dopaminergic receptors
  • Genetic variants
  • Levodopa-induced dyskinesia
  • Parkinson’s disease
  • Serotonergic receptors

ASJC Scopus subject areas

  • Pharmacology
  • Physiology

Cite this

Ivanova, S. A., Fedorenko, O. Y., Freidin, M. B., Alifirova, V. M., Zhukova, N. G., Zhukova, I. A., ... Loonen, A. J. M. (2015). Dissimilar mechanistic background of peripheral and orofacial hyperkinesia in patients with Parkinson’s disease and levodopa-induced dyskinesia. Physiology and Pharmacology, 19(4), 216-221.

Dissimilar mechanistic background of peripheral and orofacial hyperkinesia in patients with Parkinson’s disease and levodopa-induced dyskinesia. / Ivanova, Svetlana A.; Fedorenko, Olga Yu; Freidin, Maxim B.; Alifirova, Valentina M.; Zhukova, Natalia G.; Zhukova, Irina A.; Al Hadithy, Asmar F Y; Brouwers, Jacobus R B J; Bokhan, Nikolay A.; Wilffert, Bob; Loonen, Anton J M.

In: Physiology and Pharmacology, Vol. 19, No. 4, 01.12.2015, p. 216-221.

Research output: Contribution to journalArticle

Ivanova, SA, Fedorenko, OY, Freidin, MB, Alifirova, VM, Zhukova, NG, Zhukova, IA, Al Hadithy, AFY, Brouwers, JRBJ, Bokhan, NA, Wilffert, B & Loonen, AJM 2015, 'Dissimilar mechanistic background of peripheral and orofacial hyperkinesia in patients with Parkinson’s disease and levodopa-induced dyskinesia', Physiology and Pharmacology, vol. 19, no. 4, pp. 216-221.
Ivanova, Svetlana A. ; Fedorenko, Olga Yu ; Freidin, Maxim B. ; Alifirova, Valentina M. ; Zhukova, Natalia G. ; Zhukova, Irina A. ; Al Hadithy, Asmar F Y ; Brouwers, Jacobus R B J ; Bokhan, Nikolay A. ; Wilffert, Bob ; Loonen, Anton J M. / Dissimilar mechanistic background of peripheral and orofacial hyperkinesia in patients with Parkinson’s disease and levodopa-induced dyskinesia. In: Physiology and Pharmacology. 2015 ; Vol. 19, No. 4. pp. 216-221.
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T1 - Dissimilar mechanistic background of peripheral and orofacial hyperkinesia in patients with Parkinson’s disease and levodopa-induced dyskinesia

AU - Ivanova, Svetlana A.

AU - Fedorenko, Olga Yu

AU - Freidin, Maxim B.

AU - Alifirova, Valentina M.

AU - Zhukova, Natalia G.

AU - Zhukova, Irina A.

AU - Al Hadithy, Asmar F Y

AU - Brouwers, Jacobus R B J

AU - Bokhan, Nikolay A.

AU - Wilffert, Bob

AU - Loonen, Anton J M

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N2 - 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.

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