@article{e5b4f8c4125b46caadb2f37162f8f63f,
title = "Association study between multiple system atrophy and TREM2 p.R47H",
abstract = "Objective The triggering receptor expressed on myeloid cells 2 (TREM2) p.R47H substitution (rs75932628) is a risk factor for Alzheimer disease (AD) but has not been well studied in relation to the risk of multiple system atrophy (MSA); the aim of this study was to evaluate the association between the TREM2 p.R47H variant and the risk of MSA. Methods A total of 168 patients with pathologically confirmed MSA, 89 patients with clinically diagnosed MSA, and 1,695 controls were included. TREM2 p.R47H was genotyped and assessed for association with MSA. Positive results in the Taqman genotyping assay were confirmed by Sanger sequencing. The primary comparison involved patients with pathologically confirmed MSA and controls due to the definitive MSA diagnosis in the pathologically confirmed series. Results We identified TREM2 p.R47H in 3 patients with pathologically confirmed MSA (1.79%), 1 patient with clinically diagnosed MSA (1.12%), and 7 controls (0.41%). Minimal AD pathology was observed for the pathologically confirmed MSA p.R47H carriers. For the primary comparison of patients with pathologically confirmed MSA and controls, risk of disease was significantly higher for p.R47H carriers (odds ratio [OR]: 4.39, p = 0.033). When supplementing the 168 pathologically confirmed patients with the 89 clinically diagnosed and examining the combined MSA series, the association with TREM2 p.R47H remained significant (OR: 3.81, p = 0.034). Conclusions Our preliminary results suggest that the TREM2 p.R47H substitution may be a risk factor for MSA, implying a link to neuroinflammatory processes, especially microglial activation. Validation of this finding will be important, given our relatively small sample size; meta-analytic approaches will be needed to better define the role of this variant in MSA.",
author = "Kotaro Ogaki and Heckman, {Michael G.} and Shunsuke Koga and Martens, {Yuka A.} and Catherine Labb{\'e} and Oswaldo Lorenzo-Betancor and Walton, {Ronald L.} and Soto, {Alexandra I.} and Vargas, {Emily R.} and Shinsuke Fujioka and Uitti, {Ryan J.} and {Van Gerpen}, {Jay A.} and Cheshire, {William P.} and Younkin, {Steven G.} and Wszolek, {Zbigniew K.} and Low, {Phillip A.} and Wolfgang Singer and Guojun Bu and Dickson, {Dennis W.} and Ross, {Owen A.}",
note = "Funding Information: The Article Processing Charge was funded by the authors. Funding Information: K. Ogaki is supported by a research grant from the NAITO Foundation, JSPS KAKENHI Grant Number JP17K14966 and a grant from Institute for Environmental and Gender-Specific Medicine, Juntendo University. R.J. Uitti, O.A. Ross, Z.K. Wszolek, and D.W. Dickson are partially supported by the NIH/NINDS P50 NS072187. O.A. Ross is supported by the NINDS R01# NS078086, U54 NS100693, DOD W81XWH-17-1-0249, and in part by the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research. C. Labb{\'e} is the recipient of a F.R.S.Q. fellowship. Z.K. Wszolek receives research support from NIH/NIA (primary), and NIH/NINDS (secondary) 1U01AG045390-01A1, Mayo Clinic Center for Regenerative Medicine, Mayo Clinic Neuroscience Focused Research Team (Cecilia and Dan Carmichael Family Foundation, and the James C. and Sarah K. Kennedy Fund for Neurodegenerative Disease Research at Mayo Clinic in Florida), and is also partially supported by a gift from Carl Edward Bolch, Jr, and Susan Bass Bolch, The Sol Goldman Charitable Trust, and Donald G. and Jodi P. Heeringa. P.A. Low receives research support from the Cure MSA Foundation. Samples included in this study were clinical patients or brain donors to the brain bank at Mayo Clinic in Jacksonville, which is supported by the CurePSP Society for Progressive Supranuclear Palsy and Udall Center for Excellence in Parkinson Research (P50 NS072187), APDA Center for Advanced Research, an Alzheimer{\textquoteright}s disease Research Center grant (NIA P50 AG16574), and NINDS R01 NS078086. Publisher Copyright: {\textcopyright} 2018 American Academy of Neurology.",
year = "2018",
month = aug,
day = "1",
doi = "10.1212/NXG.0000000000000257",
language = "English (US)",
volume = "4",
journal = "Neurology: Genetics",
issn = "2376-7839",
publisher = "Lippincott Williams and Wilkins",
number = "4",
}