A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies

作者：Michael A. Nalls, Raquel Durán, Grisel Lopez, Marzena Kurzawa‐Akanbi, Ian G. McKeith, Patrick F. Chinnery, Christopher M. Morris, Jessie Theuns, David Crosiers, Patrick Cras, Sebastiaan Engelborghs, Peter Paul De Deyn, Christine Van Broeckhoven, David M. A. Mann, Julie S. Snowden, Stuart Pickering‐Brown, Nicola Halliwell, Yvonne S. Davidson, Linda Gibbons, Jenny Harris, Una‐Marie Sheerin, José Brás, John Hardy, Lorraine N. Clark, Karen Marder, Lawrence S. Honig, Daniela Berg, Walter Maetzler, Kathrin Brockmann, Thomas Gasser, Fabiana Novellino, Aldo Quattrone, Grazia Annesi, Elvira Valeria De Marco, Ekaterina Rogaeva, Mario Masellis, Sandra E. Black, Juan M. Bilbao, Tatiana Foroud, Bernardino Ghetti, William C. Nichols, Nathan Pankratz, Glenda M. Halliday, Suzanne Lesage, Stephan Klebe, Alexandra Dürr, Charles Duyckaerts, Alexis Brice, Benoit I. Giasson, John Q. Trojanowski, Howard I. Hurtig, Nahid Tayebi, Claudia Landazabal, Melanie A. Knight, Margaux F. Keller, Andrew Singleton, Tyra G. Wolfsberg, Ellen Sidransky · 发表于：JAMA Neurology · 年份：2013 · DOI：10.1001/jamaneurol.2013.1925 · 被引用次数：450 · 研究领域：Lysosomal Storage Disorders Research、Glycogen Storage Diseases and Myoclonus、Glycosylation and Glycoproteins Research

IMPORTANCE: While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders. OBJECTIVE: To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB). DESIGN We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate GBA1 mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity. SETTING: Eleven centers from sites around the world performing genotyping. PARTICIPANTS: Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity. MAIN OUTCOME MEASURES: Frequency of GBA1 mutations in cases and controls. RESULTS We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78-14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53-15.37). The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years...