Scientific publications

TREM2 R47H variant and risk of essential tremor: a cross-sectional international multicenter study

Ortega-Cubero S(1), Lorenzo-Betancor O(2), Lorenzo E(3), Agúndez JA(4), Jiménez-Jiménez FJ(5), Ross OA(2), Wurster I(6), Mielke C(6), Lin JJ(7), Coria F(8), Clarimon J(9), Ezquerra M(10), Brighina L(11), Annesi G(12), Alonso-Navarro H(5), García-Martin E(13), Gironell A(14), Marti MJ(10), Yueh KC(15), Wszolek ZK(16), Sharma M(6), Berg D(6), Krüger R(17), Pastor MA(18) [SP], Pastor P(19).

(1) Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra (CIMA), Pamplona, Spain; Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Instituto de Salud Carlos III, Madrid, Spain.
(2) Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
(3) Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra (CIMA), Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Instituto de Salud Carlos III, Madrid, Spain.
(4) Department of Pharmacology, University of Extremadura, Cáceres, Spain.
(5) Section of Neurology, Hospital Universitario del Sureste, Arganda del Rey, Madrid, Spain.
(6) Department for Neurodegenerative Diseases (DZNE), Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
(7) Department of Neurology, Chushang Show-Chwan Hospital, Nantou, Taiwan; Department of Neurology, Chung-Shan Medical University Hospital, Taichung, Taiwan.
(8) Department of Neurology, Son Espases University Hospital, Mallorca, Spain.
(9) Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Instituto de Salud Carlos III, Madrid, Spain; Neurology Department, Institut d'Investigacions Biomediques Sant Pau, Hospital de Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain.
(10) Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Clinic de Neurociencies, Hospital Clinic de Barcelona, CIBERNED, Barcelona, Spain.
(11) Department of Neurology, San Gerardo Hospital, Milan Center for Neuroscience, University of Milano-Bicocca, Monza, Italy.
(12) Section of Neuroimaging, Institute of Molecular Bioimaging and Physiology, National Research Council, Catanzaro, Italy.
(13) Department of Biochemistry of Molecular Biology, University of Extremadura, Cáceres, Spain.
(14) Movement Disorders Unit, Department of Neurology, Hospital de Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain.
(15) Department of Neurology, Chushang Show-Chwan Hospital, Nantou, Taiwan.
(16) Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
(17) Department for Neurodegenerative Diseases (DZNE), Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; Luxembourg Center for Systems Biomedicine, University of Luxembourg and Centre Hospitalier de Luxembourg, Luxembourg.
(18) Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Instituto de Salud Carlos III, Madrid, Spain; Neuroimaging Laboratory, Division of Neurosciences, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
(19) Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra (CIMA), Pamplona, Spain; Department of Neurology, Clínica Universidad de Navarra, University of Navarra School of Medicine, Pamplona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Instituto de Salud Carlos III, Madrid, Spain; Department of Neurology, Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain.

Magazine: Parkinsonism & Related Disorders

Date: Mar 1, 2015

Neurology [SP]

INTRODUCTION:
Essential tremor (ET) is the most frequent movement disorder in adults. Its pathophysiology is not clearly understood, however there is growing evidence showing common etiologic factors with other neurodegenerative disorders such as Alzheimer's and Parkinson's diseases (AD, PD). Recently, a rare p.R47H substitution (rs75932628) in the TREM2 protein (triggering receptor expressed on myeloid cells 2; OMIM: *605086) has been proposed as a risk factor for AD, PD and amyotrophic lateral sclerosis (ALS). The objective of the study was to determine whether TREM2 p.R47H allele is also a risk factor for developing ET. 

METHODS:
This was a cross-sectional multicenter international study. An initial case-control cohort from Spain (n = 456 ET, n = 2715 controls) was genotyped. In a replication phase, a case-control series (n = 897 ET, n = 1449 controls) from different populations (Italy, Germany, North-America and Taiwan) was studied. Owed to the rarity of the variant, published results on p.R47H allele frequency from 14777 healthy controls from European, North American or Chinese descent were additionally considered. The main outcome measure was p.R47H (rs75932628) allelic frequency. 

RESULTS:
There was a significant association between TREM2 p.R47H variant and ET in the Spanish cohort (odds ratio [OR], 5.97; 95% CI, 1.203-29.626; p = 0.042), but it was not replicated in other populations. 

CONCLUSIONS:
These results argue in favor of population-specific differences in the allelic distribution and suggest that p.R47H (rs75932628) variant may contribute to the susceptibility of ET in Spanish population. However, taking into account the very low frequency of p.R47H, further confirmatory analyses of larger ET series are needed.

CITATION  Parkinsonism Relat Disord. 2015 Mar;21(3):306-9. doi: 10.1016/j.parkreldis.2014.12.010.

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