Risk variants of the α-synuclein locus and REM sleep behavior disorder in Parkinson's disease: a genetic association study

被引：12

作者：

Bjornara, Kari Anne ^{[1
]}

Pihlstrom, Lasse ^{[2
,3
]}

Dietrichs, Espen ^{[2
,3
]}

Toft, Mathias ^{[2
,3
]}

机构：

[1] Vestre Viken Hosp Trust, Drammen Hosp, Dept Neurol, Dronninggata 21, N-3004 Drammen, Norway

[2] Oslo Univ Hosp, Dept Neurol, Oslo, Norway

[3] Univ Oslo, Inst Clin Med, Oslo, Norway

来源：

BMC NEUROLOGY | 2018年 / 18卷

关键词：

SNCA; alpha-synuclein; genetics; REM sleep behavior disorder; RBD; Parkinson's disease; BRAIN; SNCA; EXPRESSION; RELEVANCE; DEMENTIA;

D O I：

10.1186/s12883-018-1023-6

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Parkinson's disease is a heterogeneous disorder where genetic factors may underlie clinical variability. Rapid eye movement sleep behavior disorder (RBD) is a parasomnia strongly linked to synucleinopathies, including Parkinson's disease. We hypothesized that SNCA variants conferring risk of Parkinson's disease would also predispose to an RBD phenotype. Methods: We assessed possible RBD (pRBD) status using the RBD screening questionnaire and investigated known susceptibility variants for Parkinson's disease located in the a-synuclein (SNCA) and tau (MAPT) gene loci in 325 Parkinson's disease patients. Associations between genetic risk variants and RBD were investigated by logistic regression, and an independent dataset of 382 patients from the Parkinson's Progression Marker Initiative (PPMI) study was used for replication. Results: pRBD was associated with rs3756063 located in the 5' region of SNCA (two-sided p = 0.018, odds ratio 1.44). We replicated this finding in the PPMI dataset (one-sided p = 0.036, odds ratio 1.35) and meta-analyzed the results (two-sided p = 0.0032, odds ratio 1.40). The Parkinson's disease risk variant in the 3' region of SNCA and the MAPT variant showed no association with pRBD. Conclusions: Our findings provide proof of principle that a largely stable, dichotomous clinical feature of Parkinson's disease can be linked to a specific genetic susceptibility profile. Indirectly, it also supports the hypothesis of RBD as relevant marker for a distinct subtype of the disorder.

引用

页数：5

共 24 条

[1] Longitudinal assessment of probable rapid eye movement sleep behaviour disorder in Parkinson's disease [J].

Bjornara, K. A. ;

Dietrichs, E. ;

Toft, M. .

EUROPEAN JOURNAL OF NEUROLOGY, 2015, 22 (08) :1242-1244

[2] Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease [J].

Boeve, B. F. ;

Silber, M. H. ;

Saper, C. B. ;

Ferman, T. J. ;

Dickson, D. W. ;

Parisi, J. E. ;

Benarroch, E. E. ;

Ahlskog, J. E. ;

Smith, G. E. ;

Caselli, R. C. ;

Tippman-Peikert, M. ;

Olson, E. J. ;

Lin, S. -C. ;

Young, T. ;

Wszolek, Z. ;

Schenck, C. H. ;

Mahowald, M. W. ;

Castillo, P. R. ;

Del Tredici, K. ;

Braak, H. .

BRAIN, 2007, 130 :2770-2788

[3] Common variant rs356182 near SNCA defines a Parkinson's disease endophenotype [J].

Cooper, Christine A. ;

Jain, Nimansha ;

Gallagher, Michael D. ;

Weintraub, Daniel ;

Xie, Sharon X. ;

Berlyand, Yosef ;

Espay, Alberto J. ;

Quinn, Joseph ;

Edwards, Karen L. ;

Montine, Thomas ;

Van Deerlin, Vivianna M. ;

Trojanowski, John ;

Zabetian, Cyrus P. ;

Chen-Plotkin, Alice S. .

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 2017, 4 (01) :15-25

[4] Variants in GBA, SNCA, and MAPT influence Parkinson disease risk, age at onset, and progression [J].

Davis, Albert A. ;

Andruska, Kristin M. ;

Benitez, Bruno A. ;

Racette, Brad A. ;

Perlmutter, Joel S. ;

Cruchaga, Carlos .

NEUROBIOLOGY OF AGING, 2016, 37 :209.e1-209.e7

[5] Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases [J].

Gagnon, JF ;

Postuma, RB ;

Mazza, S ;

Doyon, J ;

Montplaisir, J .

LANCET NEUROLOGY, 2006, 5 (05) :424-432

[6] Parkinson's Disease Genetic Loci in Rapid Eye Movement Sleep Behavior Disorder [J].

Gan-Or, Z. ;

Girard, S. L. ;

Noreau, A. ;

Leblond, C. S. ;

Gagnon, J. F. ;

Arnulf, I. ;

Mirarchi, C. ;

Dauvilliers, Y. ;

Desautels, A. ;

Mitterling, T. ;

De Cock, V. Cochen ;

Frauscher, B. ;

Monaca, C. ;

Hogl, B. ;

Dion, P. A. ;

Postuma, R. B. ;

Montplaisir, J. Y. ;

Rouleau, G. A. .

JOURNAL OF MOLECULAR NEUROSCIENCE, 2015, 56 (03) :617-622

[7] THE RELEVANCE OF THE LEWY BODY TO THE PATHOGENESIS OF IDIOPATHIC PARKINSONS-DISEASE [J].

GIBB, WRG ;

LEES, AJ .

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1988, 51 (06) :745-752

[8] Cell type-specific genes show striking and distinct patterns of spatial expression in the mouse brain [J].

Ko, Younhee ;

Ament, Seth A. ;

Eddy, James A. ;

Caballero, Juan ;

Earls, John C. ;

Hood, Leroy ;

Price, Nathan D. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (08) :3095-3100

[9] Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database [J].

Lill, Christina M. ;

Roehr, Johannes T. ;

McQueen, Matthew B. ;

Kavvoura, Fotini K. ;

Bagade, Sachin ;

Schjeide, Brit-Maren M. ;

Schjeide, Leif M. ;

Meissner, Esther ;

Zauft, Ute ;

Allen, Nicole C. ;

Liu, Tian ;

Schilling, Marcel ;

Anderson, Kari J. ;

Beecham, Gary ;

Berg, Daniela ;

Biernacka, Joanna M. ;

Brice, Alexis ;

DeStefano, Anita L. ;

Do, Chuong B. ;

Eriksson, Nicholas ;

Factor, Stewart A. ;

Farrer, Matthew J. ;

Foroud, Tatiana ;

Gasser, Thomas ;

Hamza, Taye ;

Hardy, John A. ;

Heutink, Peter ;

Hill-Burns, Erin M. ;

Klein, Christine ;

Latourelle, Jeanne C. ;

Maraganore, Demetrius M. ;

Martin, Eden R. ;

Martinez, Maria ;

Myers, Richard H. ;

Nalls, Michael A. ;

Pankratz, Nathan ;

Payami, Haydeh ;

Satake, Wataru ;

Scott, William K. ;

Sharma, Manu ;

Singleton, Andrew B. ;

Stefansson, Kari ;

Toda, Tatsushi ;

Tung, Joyce Y. ;

Vance, Jeffery ;

Wood, Nick W. ;

Zabetian, Cyrus P. ;

Young, Peter ;

Tanzi, Rudolph E. ;

Khoury, Muin J. .

PLOS GENETICS, 2012, 8 (03)

[10] Reference-based phasing using the Haplotype Reference Consortium panel [J].

Loh, Po-Ru ;

Danecek, Petr ;

Palamara, Pier Francesco ;

Fuchsberger, Christian ;

Reshef, Yakir A. ;

Finucane, Hilary K. ;

Schoenherr, Sebastian ;

Forer, Lukas ;

McCarthy, Shane ;

Abecasis, Goncalo R. ;

Durbin, Richard ;

Price, Alkes L. .

NATURE GENETICS, 2016, 48 (11) :1443-1448

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