1. Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis
- Author
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Max Koppers, Wenhao Yu, Stefan Waibel, Rebecca D. Folkerth, Hans Scheffer, Bart P.C. van de Warrenburg, R. Jeroen Pasterkamp, Markus Weber, Helenius J. Schelhaas, John Landers, Paul I.W. de Bakker, Wim Robberecht, Bastiaan R. Bloem, Peter Heutink, Marka van Blitterswijk, Robert H. Brown, Jacobus J. van Hilten, Daniela Berg, Dagmar Verbaan, Leonard H. van den Berg, Frank P. Diekstra, Katsumi Fumoto, Patrick Lowe, Claudia Schulte, Christine Klein, Anne-Marie Wills, Jan H. Veldink, Michael A. van Es, Anneke J. van der Kooi, Hylke M. Blauw, Vincenzo Silani, Philip Van Damme, Paul W.J. van Vught, Gianni Pezzoli, Stefano Goldwurm, Rubén Fernández-Santiago, Marianne de Visser, David M. Wu, Peter M. Andersen, Ashley Lyn Leclerc, Pamela Keagle, Caroline Dahlberg, Ewout J N Groen, Wouter van Rheenen, Bart F.L. van Nuenen, Thomas Gasser, Guo-fu Hu, Albert C. Ludolph, Robin Lemmens, Nicola Ticozzi, Claudio Mariani, Edwin Cuppen, Eric A. M. Hennekam, Roel A. Ophoff, Hiroko Kishikawa, Anna Birve, Amsterdam Neuroscience, Neurology, Amsterdam Cardiovascular Sciences, Neurosurgery, Human genetics, NCA - Neurodegeneration, and Hubrecht Institute for Developmental Biology and Stem Cell Research
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Male ,medicine.medical_specialty ,Pathology ,Neurology ,statistics & numerical data [Databases, Factual] ,Angiogenin ,genetics [Ribonuclease, Pancreatic] ,Functional Neurogenomics Human Movement & Fatigue [DCN 2] ,Genome-wide association study ,Genomic disorders and inherited multi-system disorders Functional Neurogenomics [IGMD 3] ,Disease ,Gene mutation ,genetics [Parkinson Disease] ,medicine ,Humans ,Multicenter Studies as Topic ,Dementia ,Genetic Predisposition to Disease ,In patient ,ddc:610 ,Amyotrophic lateral sclerosis ,business.industry ,Ribonuclease, Pancreatic ,medicine.disease ,genetics [Genetic Variation] ,United States ,Europe ,genetics [Amyotrophic Lateral Sclerosis] ,cardiovascular system ,Female ,Neurology (clinical) ,business ,angiogenin - Abstract
Contains fulltext : 95644.pdf (Publisher’s version ) (Closed access) 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 x 10(-6) for ALS and p = 4.3 x 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. ANN NEUROL 2011;70:964-973. 01 december 2011 10 p.
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- 2011
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