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Large-scale assessment of polyglutamine repeat expansions in Parkinson disease

2015; Lippincott Williams & Wilkins; Volume: 85; Issue: 15 Linguagem: Inglês

10.1212/wnl.0000000000002016

1526-632X

Lisa Wang, Jan Aasly, Grazia Annesi, Soraya Bardien, Maria Bozi, Alexis Brice, Jonathan Carr, Sun Ju Chung, Carl E Clarke, David Crosiers, Angela Deutschländer, Gertrud Eckstein, Matthew J. Farrer, Stefano Goldwurm, Gaëtan Garraux, Georgios M. Hadjigeorgiou, Andrew A. Hicks, Nobutaka Hattori, Christine Klein, Beom S. Jeon, Yun Joong Kim, Suzanne Lesage, Juei-Jueng Lin, Timothy Lynch, Peter Lichtner, Anthony E. Lang, Vincent Mok, Barbara Jasińska‐Myga, George D. Mellick, Karen Morrison, Grzegorz Opala, Lasse Pihlstrøm, Peter P. Pramstaller, Sung S. Park, Aldo Quattrone, Ekaterina Rogaeva, Owen A. Ross, Leonidas Stefanis, Joanne Stockton, Peter A. Silburn, Jessie Theuns, Eng King Tan, Hiroyuki Tomiyama, Mathias Toft, Christine Van Broeckhoven, Ryan J. Uitti, Karin Wirdefeldt, Zbigniew K. Wszołek, Georgia Xiromerisiou, Kuo-Chu Yueh, Yi Zhao, Thomas Gasser, Demetrius M. Maraganore, Rejko Krüger, Manu Sharma, R.S Boyle, A Sellbach, John D. O’Sullivan, Greg T. Sutherland, G. Siebert, N. Dissanayaka, Christine Van Broeckhoven, Jessie Theuns, David Crosiers, Barbara Pickut, Sebastiaan Engelborghs, Bram Meeus, Peter Paul De Deyn, Patrick Cras, Ekaterina Rogaeva, Anthony E. Lang, Christophe Tzourio, Philippe Amouyel, Marie‐Anne Loriot, Eugénie Mutez, Aurélie Duflot, Jean-Philippe Legendre, Nawal Waucquier, Thomas Gasser, Olaf Rieß, Daniela Berg, Claudia Schulte, Christine Klein, Ana Djarmati, Johann Hagenah, Katja Lohman, Georg Auburger, Rüdiger Hilker, Simone van de Loo, Efthimios Dardiotis, Vaïa Tsimourtou, Styliani Ralli, Persa Kountra, Gianna Patramani, Cristina Vogiatzi, Nobutaka Hattori, Hiroyuki Tomiyama, Manabu Funayama, Hiroyo Yoshino, Yuanzhe Li, Yoko Imamichi, Tatsushi Toda, Wataru Satake, Tim Lynch, Enza Maria Valente, Alessandro Ferraris, Bruno Dallapiccola, Tàmara Ialongo, Laura Brighina, B. Corradi, Carlo Ferrarese, Monza Roberto Piolti, Patrizia Tarantino, Ferdinanda Annesi, Monica Gagliardi, Patrizia Tarantino, Beom S. Jeon, Sung Sup Park, Jan Aasly, Grzegorz Opala, Barbara Jasińska‐Myga, Gabriela Kłodowska-Duda, Magdalena Boczarska‐Jedynak, Eng King Tan, Andrea Carmine Belin, Lar̀s Olson, Dagmar Galter, Marie Westerlund, Olof Sydow, Christer Nilsson, Andreas Puschmann, J-J Lin, Demetrius M. Maraganore, J. Eric Ahlskog, Mariza de Andrade, Timothy G. Lesnick, Walter A. Rocca, Harvey Checkoway, Owen A. Ross, Zbigniew K. Wszołek, Ryan J. Uitti,

Neurological disorders and treatments

Objectives: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). Methods: We invited researchers from the Genetic Epidemiology of Parkinson9s Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. Results: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. Conclusions: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD.