Document Detail

Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis.
MedLine Citation:
PMID:  22190368     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.
METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios.
RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD.
INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.
Michael A van Es; Helenius J Schelhaas; Paul W J van Vught; Nicola Ticozzi; Peter M Andersen; Ewout J N Groen; Claudia Schulte; Hylke M Blauw; Max Koppers; Frank P Diekstra; Katsumi Fumoto; Ashley Lyn LeClerc; Pamela Keagle; Bastiaan R Bloem; Hans Scheffer; Bart F L van Nuenen; Marka van Blitterswijk; Wouter van Rheenen; Anne-Marie Wills; Patrick P Lowe; Guo-fu Hu; Wenhao Yu; Hiroko Kishikawa; David Wu; Rebecca D Folkerth; Claudio Mariani; Stefano Goldwurm; Gianni Pezzoli; Philip Van Damme; Robin Lemmens; Caroline Dahlberg; Anna Birve; Rubén Fernández-Santiago; Stefan Waibel; Christine Klein; Markus Weber; Anneke J van der Kooi; Marianne de Visser; Dagmar Verbaan; Jacobus J van Hilten; Peter Heutink; Eric A M Hennekam; Edwin Cuppen; Daniela Berg; Robert H Brown; Vincenzo Silani; Thomas Gasser; Albert C Ludolph; Wim Robberecht; Roel A Ophoff; Jan H Veldink; R Jeroen Pasterkamp; Paul I W de Bakker; John E Landers; Bart P van de Warrenburg; Leonard H van den Berg
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Annals of neurology     Volume:  70     ISSN:  1531-8249     ISO Abbreviation:  Ann. Neurol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-22     Completed Date:  2012-02-09     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  964-73     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 American Neurological Association.
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MeSH Terms
Amyotrophic Lateral Sclerosis / genetics*
Databases, Factual / statistics & numerical data
Genetic Predisposition to Disease*
Genetic Variation / genetics*
Multicenter Studies as Topic
Parkinson Disease / genetics*
Ribonuclease, Pancreatic / genetics*
United States
Grant Support
1R01NS065847/NS/NINDS NIH HHS; 5P50AG005134-27/AG/NIA NIH HHS; 5U10NS053369-05/NS/NINDS NIH HHS; GTB07001//Telethon; R01MH084676/MH/NIMH NIH HHS
Reg. No./Substance:
EC 3.1.27.-/angiogenin; EC, Pancreatic
Comment In:
Ann Neurol. 2012 May;71(5):725-7; author reply 727-8   [PMID:  22522484 ]

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