The impact of DRD3, HS1-BP3, and LINGO1 gene mutations on the development and clinical heterogeneity of essential tremor in the Sakha Republic (Yakutia)

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Abstract

Introduction. The ETM1, ETM2 and ETM3 loci are linked with the development of essential tremor (ET). It has been established that a mutation in the LINGO1 gene is a significant risk factor for ET development.

The aim of the study was to investigate the role of Ser9Gly polymorphism in the DRD3 gene, the Ala265Gly mutation in the HS1-BP3 gene and rs9652490 polymorphism in the LINGO1 gene in the development and clinical heterogeneity of ET in the Sakha Republic population (Yakutia).

Materials and methods. Thirty-nine patients with a confirmed diagnosis of ET and 48 patients with Parkinson disease were examined. The control group consisted of 87 healthy individuals. Polymorphism carrier status and gene mutations were identified using real-time polymerase chain reaction.

Results. The Ser/Gly genotype with Ser9Gly polymorphism in the DRD3 gene and the A/A genotype with rs9652490 polymorphism in the LINGO1 gene increases the risk of developing ET by 2.35 (p = 0.02) and 2.42 (p = 0.04) times, respectively. Moreover, the A/A genotype of the rs9652490 in the LINGO1 gene increases the risk for ET-plus syndrome by 2.17 times (p = 0.02). Our data didn’t confirm the role of the Ala265Gly mutation in the HS1-BP3 gene in development of the ET.

About the authors

Tatyana G. Govorova

M.K. Ammosov North-Eastern Federal University, Yakutsk

Author for correspondence.
Email: platonova@neurology.ru
Russian Federation

Tatyana E. Popova

M.K. Ammosov North-Eastern Federal University, Yakutsk

Email: platonova@neurology.ru
Russian Federation

Alexey A. Tappakhov

M.K. Ammosov North-Eastern Federal University, Yakutsk

Email: platonova@neurology.ru
Russian Federation

Polina I. Golikova

M.K. Ammosov North-Eastern Federal University, Yakutsk

Email: platonova@neurology.ru
Russian Federation

Anastasya L. Danilova

M.K. Ammosov North-Eastern Federal University, Yakutsk

Email: platonova@neurology.ru
Russian Federation

Ulyana D. Antipina

M.K. Ammosov North-Eastern Federal University, Yakutsk

Email: platonova@neurology.ru
Russian Federation

Vera N. Samorseva

ФГАОУ ВО «Северо-Восточный федеральный университет им. М.К. Аммосова», Якутск

Email: platonova@neurology.ru
Russian Federation

Alena Yu. Petrova

Republican Hospital No. 2 — Center for Emergency Medical Care, Yakutsk

Email: platonova@neurology.ru
Russian Federation

Michil E. Andreev

M.K. Ammosov North-Eastern Federal University, Yakutsk

Email: platonova@neurology.ru
Russian Federation

Nadezhda N. Lyasheeva

Yakutsk Medical Center, Yakuts

Email: platonova@neurology.ru
Russian Federation

References

  1. Louis E.D., Ferreira J.J. How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor. Mov Disord 2010; 25: 534–541. doi: 10.1002/mds.22838. PMID: 20175185.
  2. Clark L.N., Louis E.D. Challenges in essential tremor genetics. Rev Neurol (Paris) 2015; 171: 466–474. doi: 10.1016/j.neurol.2015.02.015. PMID: 26003805.
  3. Louis E.D. Environmental epidemiology of essential tremor. Neuroepidemiology 2008; 31: 139–149. doi: 10.1159/000151523. PMID: 18716411.
  4. Louis E.D., Ottman R. Study of possible factors associated with age of onset in essential tremor. Mov Disord 2006; 21: 980–1986. doi: 10.1002/mds.21102. PMID: 16991147.
  5. Wider C., Ross O.A., Wszolek Z.K. Genetics of Parkinson disease and essential tremor. Curr Opin Neurol 2010; 23: 388–393. doi: 10.1097/WCO.0b013e32833b1f4c. PMID: 20489616.
  6. Bain P.G., Findley L.J., Thompson P.D. et al. A study of hereditary essential tremor. Brain 1994; 117: 805–824. doi: 10.1093/brain/117.4.805. PMID: 7922467.
  7. Clark L.N., Louis E.D. Essential tremor. Handb Clin Neurol 2018; 147: 229–239. doi: 10.1016/B978-0-444-63233-3.00015-4. PMID: 29325613.
  8. Deng H., Le W., Jankovic J. Genetics of essential tremor. Brain 2007; 130: 1456–1464. doi: 10.1093/brain/awm018. PMID: 17353225.
  9. Gulcher J.R., Jónsson P., Kong A. et al. Mapping of a familial essential tremor gene, FET1, to chromosome 3q13. Nat Genet 1997; 17: 84–87. doi: 10.1038/ng0997-84. PMID: 9288103.
  10. Higgins J.J., Pho L.T., Nee L.E. et al. A gene for essential tremor maps to chromosome 2p22-p25. Mov Disord 1997; 12: 859–864. doi: 10.1002/mds.870120605. PMID: 9399207.
  11. Shatunov A., Jankovic J., Elble R. et al. A variant in the HS1-BP3 gene is associated with. Neurology 2005; 65: 1995–1997. doi: 10.1212/01.wnl.0000200984.10076.e5. PMID: 16380635.
  12. Stefansson H., Steinberg S, Petursson H. et al. Variant in the sequence of the LINGO1 gene confers risk of essential tremor. Nat Genet 2009; 41: 277–279. doi: 10.1038/ng.299. PMID: 19182806.
  13. Wu Y.R., Rong T., Li H. et al. Analysis of Lingo1 variant in sporadic and familial essential tremor among Asians Genet. Acta Neurol Scand 2011: 124: 264–268. doi: 10.1111/j.1600-0404.2010.01466.x. PMID: 21158743.
  14. Jiménez-Jiménez F.J., García-Martín E., Lorenzo-Betancor O. et al. LINGO1 and risk for essential tremor: Results of a meta-analysis of rs9652490 and rs11856808. J Neurol Sci 2012; 317: 52–57. doi: 10.1016/j.jns.2012.02.030. PMID: 22425540.
  15. Bourassa C.V., Rivière J.B., Dion P.A. et al. LINGO1 Variants in the French-Canadian Population. PLoS One 2011; 6: 1–3. doi: 10.1371/journal.pone.0016254. PMID: 21264305.
  16. Radovica I., Inashkina I., Smeltere L. et al. Screening of 10 SNPs of LINGO1 gene in patients with essential tremor in the Latvian population. Parkinsonism Relat Disord 2012; 18: 93–95. doi: 10.1016/j.parkreldis.2011.06.006. PMID: 21741293.
  17. Vilariño-Güell C., Wider C., Ross O.A. et. al. LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease. Neurogenetics 2010; 11: 401–408. doi: 10.1007/s10048-010-0241-x. PMID: 20369371.
  18. Lucotte G., Lagarde J.P., Funalot B. et al. Linkage with the Ser9Gly DRD3 polymorphism in essential tremor families. Clin Genet 2006; 69: 437–440. doi: 10.1111/j.1399-0004.2006.00600.x. PMID: 16650084.
  19. García-Martín E., Martínez C., Alonso-Navarro H. et al. Dopamine receptor D3 (DRD3) genotype and allelic variants and risk for essential tremor. Mov Disord 2009; 24: 1910–1915. PMID: 19645064. doi: 10.1002/mds.22518.
  20. Jeanneteau F., Funalot B., Jankovic J. et al. A functional variant of the dopamine D3 receptor is associated with risk and age-at-onset of essential tremor. Proc Natl Acad Sci 2006; 103: 10753–10758. doi: 10.1073/pnas.0508189103. PMID: 16809426.
  21. Tarasova E.N., Ivanova-Smolenskaya I.A., Karabanov A.V. et al. [Molecular genetics of essential tremor]. In: Materialy I Natsionalnogo kongressa «Bolezn’ Parkinsona i rasstroystva dvizheniy». Moscow, 2008: 80–83. (In Russ.)
  22. Shatunov A., Jankovic J., Elble R. et al. A variant in the HS1-BP3 gene is associated with familial essential tremor. Neurology 2005; 65: 1995. doi: 10.1212/01.wnl.0000200984.10076.e5. PMID: 16380635.
  23. Higgins J.J., Pho L.T., Nee L.E. et al. A gene for essential tremor maps to chromosome 2p22-p25. Mov Disord 1997; 12: 859–864. doi: 10.1002/mds.870120605. PMID: 9399207.
  24. Tan E.K. LINGO1 and essential tremor: linking the shakes. Linking LINGO1 to essential tremor. Eur J Hum Genet 2010; 18: 739–740. doi: 10.1038/ejhg.2010.25. PMID: 20372187.
  25. Vilariño-Güell C., Wider C., Ross O.A. et al. LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease. Neurogenetics 2010; 11: 401–408. doi: 10.1007/s10048-010-0241-x. PMID: 20369371.

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Copyright (c) 2020 Govorova T.G., Popova T.E., Tappakhov A.A., Golikova P.I., Danilova A.L., Antipina U.D., Samorseva V.N., Petrova A.Y., Andreev M.E., Lyasheeva N.N.

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