pISSN 1907-3062 | eISSN 2407-2230 | Universa Medicina content is searchable on DOAJ, Google Scholar, and OAI

Propranolol decreases DRD3 and SLC1A2 gene expression in patients with essential tremor

Nefise Kandemir, Murat Gultekin, Mehmet Kara, Arslan Bayram, Nazife Tascioglu, Meral Mirza, Munis Dundar
Submission date: Monday, 16 March 2020
Published date: Thursday, 23 July 2020
DOI: http://dx.doi.org/10.18051/UnivMed.2020.v39.105-112

Article Metrics

Abstract viewed: 143 times


Essential tremor (ET) is the most common disease among movement disorders. Genes such as essential tremor 1-4 (ETM 1-4), HS1-binding protein-3 (HS1BP3), dopamine receptor D3 (DRD3), leucine-rich repeat and Ig domain containing 1 (LINGO1), glial high affinity glutamate transporter member 2 (SLC1A2), FUS, high temperature requirement A2 (HTRA2) and TENM4 had been shown to be responsible for the genetic inheritance of the disease. The aim of the present study was to investigate the effect of propranolol on the expression of DRD3, SLC1A2, and HTRA2 genes in patients with ET.

A study of non-randomized experimental design was conducted involving 76 subjects. They were divided into two groups: 38 patients with ET in the patient group (Group 1) and 38 healthy people in the control group (Group 2). DRD3, SLC1A2 and HTRA2 gene expressions were assessed before and after 8 weeks of propranolol treatment. Fahn-Tolosa-Marin tremor scale results were compared before and after propranolol administration. Kruskal Wallis test was used to determine differences in gene expressions between the groups.

D3 dopamine receptor and SLC1A2 gene expression in the patient group appeared to be lower than in the control group (p<0.001). However, the HTRA2 gene expression level was significantly higher in the patient group (p<0.001).

D3 dopamine receptor and SLC1A2 gene expressions were decreased in ET patients which at first glance can be explained in relation to etiology, but after treatment it was not increased as expected but decreased even more.


Essential tremor; Propranolol; DRD3; SLC1A2; HTRA2; Gene expression

Full Text:



Kuhlenbäumer G, Hopfner F, Deuschl G. Genetics of essential tremor: meta-analysis and review. Neurology 2014;82:1000-7. doi: 10.1212/WNL.0000000000000211.

Louis ED, Ferreira JJ. How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor. Mov Disord 2010;25:534-41. doi:10.1002/mds.22838.

Pahwa R, Dhall R, Ostrem J, et al. An acute randomized controlled trial of noninvasive peripheral nerve stimulation in essential tremor. Neuromodulation 2019; 22: 537–45. doi: 10.1111/ner.12930.

Prasad S, Bhalsing KS, Jhunjhunwala K, Lenka A, Binu V, Pal PK. Phenotypic variability of essential tremor based on the age at onset. Can J Neurol Sci 2019;46:192-8. doi: 10.1017/cjn.2018.384.

Agarwal S, Biagioni MC. Essential tremor. Treasure Island (FL): StatPearls Publishing; 2020

Benito‐León J, Serrano JI, Louis ED, et al. Essential tremor severity and anatomical changes in brain areas controlling movement sequencing. Ann Clin Trans Neurol 2019;6:83-97. doi: 10.1002/acn3.681.

Vogelnik K, Kojovic M. From beta‐blockers to Parkinson's disease in respect of essential tremor. Mov Disord 2019;34:153.doi: 10.1002/mds.27586.

Prasad S, Pal PK. Reclassifying essential tremor: Implications for the future of past research. Mov Disord 2019;34:437.doi: 10.1002/mds.27615.

Musacchio T, Purrer V, Papagianni A, etal. Non-motor symptoms of essential tremor are independent of tremor severity and have an impact on quality of life. Tremor Other Hyperkinet Mov 2016; 6:361. doi:10.7916/D8542NCH.

Bermejo-Pareja F, Puertas-Martın V. Cognitive features of essential tremor: a review of the clinical aspects and possible mechanistic underpinnings. Tremor Other Hyperkinet Mov 2012;02-74-541-1. doi: 10.7916/D89W0D7W.

Benito-Leon J, Louis ED, Bermejo-Pareja F. Short sleep duration heralds essential tremor: a prospective, population-based study. Mov Disord 2013;28:1700–7. doi: http://dx.doi.org/10.1002/mds.25590.

Clark LN, Louis ED. Challenges in essential tremor genetics. Rev Neurol (Paris) 2015 ; 171: 466–74. doi:10.1016/j.neurol.2015.02.015.

Cristal AD, Chen KP, Hernandez NC, et al. Knowledge about essential tremor: a study of essential tremor families. Front Neurol 2018; 9:27.doi: 10.3389/fneur.2018.00027.

Deuschl G, Raethjen J, Hellriegel H, Elble R. Treatment of patients with essential tremor. Lancet Neurol 2011;10:148–61. DOI:https://doi.org/10.1016/S1474-4422(10)70322-7.

Rajput AH, Rajput A. Medical treatment of essential tremor. J Cent Nerv Syst Dis 2014;6: 29–39. doi: 10.4137/JCNSD.S13570. 16. Deuschl G, Raethjen J, Hellriegel H, Elble R. Treatment of patients with essential tremor. Lancet Neurol 2011;10:148-61. Doi: 10.1016/S1474-4422(10)70322-7.

Prieto GA. Abnormalities of dopamine D3 receptor signaling in the diseased brain. J Cent Nerv Syst Dis 2017;9: 1–8. DOI: 10.1177/1179573517726335.

Lee M, Cheng MM, Lin CY, Louis ED, Faust PL,Kuo SH. Decreased EAAT2 protein expression in the essential tremor cerebellar cortex. Acta Neuropathol Commun 2014, 2:157. doi:10.1186/s40478-014-0157-z.

Shao L, Vawter MP. Shared gene expression alterations in schizophrenia and bipolar disorder. Biol Psychiatry 2008; 64: 89–97. doi: 10.1016/j.biopsych.2007.11.010.

Desideri E, Martins LM. Mitochondrial stress signalling: HTRA2 and Parkinson’s disease. International J Cell Biol 2012, Article ID 607929, 6 pages. doi:10.1155/2012/607929.

Zesiewicz TA, Chari A, Jahan I, Miller AM, Sullivan KL. Overview of essential tremor. Neuropsychiatr Dis Treat 2010;6:401. Doi: 10.2147/ndt.s4795.

Hu Q, Wang G. Mitochondrial dysfunction in Parkinson’s disease. Transl Neurodegeneration 2016; 5:14. DOI 10.1186/s40035-016-0060-6.

He YC, Huang P, Li QQ, et al. Mutation analysis of HTRA2 gene in Chinese familial essential tremor and familial Parkinson’s disease. Parkinson’s Dis 2017;2017: 3217474. Doi: 10.1155/2017/3217474.

Jiménez-Jiménez FJ, García-Martín E, Alonso-Navarro H, , et al. A family study of DRD3 rs6280, SLC1A2 rs3794087 and MAPT rs1052553 variants in essential tremor. Neurol Res 2016;38:880-7. Doi: 10.1080/01616412.2016.1210355.

Fahn S, Tolosa E, Marín C. Clinical rating scale for tremor. In: Jankovic J, Tolosa E, editors. Parkinson’s Disease and Movement Disorders. 2nd. ed. Baltimore: Williams & Wilkins; 1993. p. 225-34.

Cormier F, Muellner J, Corvol JC. Genetics of impulse control disorders in Parkinson’s disease. J Neural Transm 2013; 120:665–71. DOI 10.1007/s00702-012-0934-4.

Sokoloff P, Foll BL. The dopamine D3 receptor, a quarter century later. Eur J Neurosci 2017; 45: 2–19.

Caravaggio F, Borlido C, Wilson A, Graff-Guerrero A. Examining endogenous dopamine in treated schizophrenia using [11C]-(+)-PHNO positron emission tomography: a pilot study. Clin Chim Acta 2015; 449:60–2. doi: 10.1016/j.cca.2015.03.020..

Delay C, Tremblay C, Brochu E, et al. Increased LINGO1 in the cerebellum of essential tremor patients. Mov Disord 2014;29:1637-47. https://doi.org/10.1002/mds.25819.

Gulsuner HU, Gulsuner S, Mercan FN, et al. Mitochondrial serine protease HTRA2 p. G399S in a kindred with essential tremor and Parkinson disease. Proc Natl Acad Sci U S A

;111:18285-90. doi: 10.1073/pnas.1419581111.

Goo HG, Jung MK, Han SS, Rhim H, Kang S. HtrA2/Omi deficiency causes damage and mutation of mitochondrial DNA. Biochimica et Biophysica Acta 2013;1833: 1866–75 .http://dx.doi.org/10.1016/j.bbamcr.2013.03.016

Shori TD, Rezaeianyazdi S, Lana E, et al. Increased active OMI/HTRA2 serine protease displays a positive correlation with cholinergic alterations in the Alzheimer’s disease brain. Mol Neurobiol 2019; 56:4601–19. https://doi.org/10.1007/s12035-018-1383-3.

Salehifar E, Ebrahim S, Shiran MR, et al. Pharmacokinetic parameters and over-responsiveness of Iranian population to propranolol. Adv Pharm Bull 2017; 7: 195-202. doi: 10.15171/apb.2017.024.


  • There are currently no refbacks.

Copyright (c) 2020 Nefise Kandemir, Murat Gultekin, Mehmet Kara, Arslan Bayram, Nazife Tascioglu, Meral Mirza, Munis Dundar

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Creative Commons License
Universa Medicina by Faculty of Medicine, Trisakti University is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Based on a work at https://univmed.org/ejurnal/index.php/medicina/