Ortega-Cubero Sara, Lorenzo-Betancor Oswaldo, Lorenzo Elena, Agúndez José A G, Jiménez-Jiménez Félix J, Ross Owen A, Wurster Isabel, Mielke Carina, Lin Juei-Jueng, Coria Francisco, Clarimon Jordi, Ezquerra Mario, Brighina Laura, Annesi Grazia, Alonso-Navarro Hortensia, García-Martin Elena, Gironell Alex, Marti Maria J, Yueh Kuo-Chu, Wszolek Zbigniew K, Sharma Manu, Berg Daniela, Krüger Rejko, Pastor Maria A, Pastor Pau
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 Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Parkinsonism Relat Disord. 2015 Mar;21(3):306-9. doi: 10.1016/j.parkreldis.2014.12.010. Epub 2014 Dec 24.
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.
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.
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.
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.
特发性震颤（ET）是成年人中最常见的运动障碍。其病理生理学尚未完全明确，但越来越多的证据表明，它与阿尔茨海默病和帕金森病（AD、PD）等其他神经退行性疾病存在共同的病因学因素。最近，髓系细胞触发受体2（TREM2；OMIM：*605086）蛋白中一种罕见的p.R47H替代（rs75932628）被认为是AD、PD和肌萎缩侧索硬化症（ALS）的危险因素。本研究的目的是确定TREM2 p.R47H等位基因是否也是ET发病的危险因素。
这是一项横断面多中心国际研究。对来自西班牙的一个初始病例对照队列（456例ET患者，2715例对照）进行基因分型。在复制阶段，研究了来自不同人群（意大利、德国、北美和台湾）的一个病例对照系列（897例ET患者，1449例对照）。由于该变异罕见，还额外考虑了来自欧洲、北美或中国血统的14777名健康对照中p.R47H等位基因频率的已发表结果。主要观察指标是p.R47H（rs75932628）等位基因频率。
在西班牙队列中，TREM2 p.R47H变异与ET之间存在显著关联（优势比[OR]，5.97；95%可信区间，1.203 - 29.626；p = 0.042），但在其他人群中未得到重复验证。
这些结果支持等位基因分布存在人群特异性差异的观点，并表明p.R47H（rs75932628）变异可能与西班牙人群中ET的易感性有关。然而，考虑到p.R47H的频率非常低，需要对更大规模的ET系列进行进一步的验证分析。
