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The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients.

Title: The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients.
Authors: Metzger, Silke; Walter, Carolin; Riess, Olaf; Nguyen, Huu Phuc; Bachoud-Lévi, Anne-Catherine; Bentivoglio, Anna Rita; Biunno, Ida; Bonelli, Raphael M; Burgunder, Jean-Marc; Ferreira, Joaquim J; Heiberg, Arvid; Illmann, T; Landwehrmeyer, G Bernhard; Levey, John; Ramos-Arroyo, Maria A; Nielsen, Jørgen; Koivisto, Susana Pro; Päivärinta, Markku; Roos, Raymund A C; Sebastián, Ana Rojo; Tabrizi, Sarah; Vandenberghe, Wim; Verellen-Dumoulin, Christine; Zaremba, Jacek; Uhrová, Tereza; Wahlström, Jan; Barth, Katrin; Correia-Guedes, Leonor; Finisterra, Ana Maria; Garde, Monica Bascuñana; Bos, Reineke; Betz, Sabrina; Callaghan, Jenny; Fullam, Ruth; Ecker, Daniel; Nielsen, Mette Gilling; Hvalstedt, Carina; Held, Christine; Koppers, Kerstin; Laurà, Matilde; Horta, Saul Martinez; Descals, Asunción Martínez; Díaz, Madrid-Fundación Jiménez; Mestre, Tiago; Minster, Sara; Monza, Daniela; Mütze, Lisanne; Oehmen, Martin; Townhill, Jenny; Orth, Michael; Padieu, Helene; Paterski, Laurent; Peppa, Nadia; Roedig, Verena; Rialland, Amandine; Røren, Niini; Šašinková, Pavla; Seliverstov, Yury; Cubillo, Patricia Trigo; van Walsem, Marleen R; Wright, Abigail; Silva, Wildson Vieira da; Witjes-Anné, Marie-Noelle; Yudina, Elizaveta; Zielonka, Daniel; Zielonka, Eugeniusz; Zinzi, Paola; Herranhof, Brigitte; Holl, Anna; Kapfhammer, Hans-Peter; Koppitz, Michael; Magnet, Markus; Otti, Daniela; Painold, Annamaria; Reisinger, Karin; Scheibl, Monika; Hecht, Karen; Lilek, Sabine; Müller, Nicole; Schöggl, Helmut; Ullah, Jasmin; Ribaï, Pascale; Boogaerts, Andrea; van Reijen, Dimphna; Klempíř, Jiří; Majerová, Veronika; Roth, Jan; Hjermind, Lena; Jacobsen, Oda; Vinthev-Jensen, Tua; Larsen, Ida Unmack; Stockholm, Jette; Hiivola, Heli; Martikainen, Kirsti; Tuuha, Katri; Ignatius, Jaakko; Kärppä, Mikko; Åman, Jaana; Mustonen, Aki; Kajula, Outi; Santala, Maire; Allain, Philippe; Guérid, Marie-Anne; Gohier, Bénédicte; Olivier, Audrey; Prundean, Adriana; Scherer-Gagou, Clarisse; Verny, Christophe; Bost, Marie; Babiloni, Blandine; Debruxelles, Sabrina; Duché, Charlotte; Goizet, Cyril; Lafoucrière, Danielle; Jameau, Laetitia; Spampinato, Umberto; De Bruycker, Christelle; Cabaret, Maryline; Carette, Anne-Sophie; Defebvre, Luc; Decorte, Eric; Delval, Arnaud; Delliaux, Marie; Destee, Alain; Dujardin, Kathy; Peter, Mireille; Plomhouse, Lucie; Sablonnière, Bernard; Simonin, Clémence; Lemaire, Marie-Hélène; Manouvrier, Sylvie; Thibault-Tanchou, Stéphanie; Vuillaume, Isabelle; Krystkowiak, Pierre; Duru, Cécile; Roussel, Martine; Wannepain, Sandrine; Berrissoul, Hassan; Bellonet, Marcellin; Courtin, Françoise; Mantaux, Béatrice; Fasquel, Véronique; Godefroy, Olivier; Azulay, Jean-Philippe; Fluchère, Frédérique; Delfini, Marie; Eusebio, Alexandre; Mundler, Laura; Longato, Nadine; Rudolf, Gabrielle; Steinmetz, Gisèle; Tranchant, Christine; Wagner, Caroline; Zimmermann, Marie-Agathe; Marcel, Christophe; Andrich, Jürgen; Ellrichmann, Gisa; Hoffmann, Rainer; Kaminski, Barbara; Saft, Carsten; Stamm, Christiane; Boelmans, Kai; Ganos, Christos; Goerendt, Ines; Hidding, Ute; Lewerenz, Jan; Münchau, Alexander; Schmalfeld, Jenny; Stubbe, Lars; Zittel, Simone; Bürk, Kathrin; Möller, Jens Carsten; Rissling, Ida; Cormio, Claudia; Sciruicchio, Vittorio; Serpino, Claudia; de Tommaso, Marina; Capellari, Sabina; Cortelli, Pietro; Gallassi, Roberto; Poda, Roberto; Rizzo, Giovanni; Scaglione, Cesa; Abbruzzese, Giovanni; di Poggio, Monica Bandettini; Di Maria, Emilio; Ferrandes, Giovanna; Mandich, Paola; Marchese, Roberta; Albanese, Alberto; Di Bella, Daniela; Di Donato, Stefano; Gellera, Cinzia; Genitrini, Silvia; Mariotti, Caterina; Nanetti, Lorenzo; Paridi, Dominga; Soliveri, Paola; Tomasello, Chiara; Squitieri, Ferdinando; Elifani, Francesca; Maglione, Vittorio; Di Pardo, Alba; Alberti, Silvia; Griguoli, Annamaria; Amico, Enrico; Martino, Tiziana; Petrollini, Martina; Catalli, Claudio; Di Giacopo, Raffaella; Fasano, Alfonso; Frontali, Marina; Guidubaldi, Arianna; Ialongo, Tamara; Jacopini, Gioia; Loria, Giovanna; Piano, Carla; Chiara, Piccininni; Quaranta, Davide; Romano, Silvia; Soleti, Francesco; Spadaro, Maria; van Hout, Monique S E; van Vugt, Jeroen P P; de Weert, A Marit; Bolwijn, J J W; Dekker, M; Leenders, K L; Dumas, Eve M; van den Bogaard, Simon J A; 't Hart, Ellen P; van Duijn, Erik; Kremer, Berry; Verstappen, C C P; Blinkenberg, Ellen Økland; Hauge, Erik; Tyvoll, Hilde; Frich, Jan; Aaserud, Olaf; Wehus, Raghild; Bjørgo, Kathrine; Fannemel, Madeleine; Gørvell, Per; Lorentzen, Eirin; Retterstøl, Lars; Overland, Torborg; Stokke, Bodil; Bjørnevoll, Inga; Sando, Sigrid Botne; Dziadkiewicz, Artur; Nowak, Malgorzata; Robowski, Piotr; Sitek, Emilia; Slawek, Jaroslaw; Soltan, Witold; Szinwelski, Michal; Blaszcyk, Magdalena; Boczarska-Jedynak, Magdalena; Ciach-Wysocka, Ewelina; Gorzkowska, Agnieszka; Jasinska-Myga, Barbara; Opala, Gregorz; Kłodowska-Duda, Gabriela; Stompel, Daniel; Banaszkiewicz, Krzysztof; Boćwińska, Dorota; Szczudlik, Andrzej; Rudzinska, Monika; Wójcik, Magdalena; Dec, Małgorzata; Krawczyk, Malgorzata; Bojakowska-Jaremek, Kamila; Szczygieł, Elżbieta; Stenwak, Agata; Wasielewska, Anna; Bryl, Anna; Ciesielska, Anna; Klimberg, Aneta; Marcinkowski, Jerzy; Sempołowicz, Justyna; Samara, Husam; Wiśniewski, Bartłomiej; Janik, Piotr; Gogol, Anna; Kwiecinski, Hubert; Jamrozik, Zygmunt; Kaminska, Anna; Antczak, Jakub; Jachinska, Katarzyna; Rakowicz, Maryla; Richter, Przemyslaw; Rola, Rafal; Ryglewicz, Danuta; Sienkiewicz-Jarosz, Halina; Stępniak, Iwona; Witkowski, Grzegorz; Zdzienicka, Elzbieta; Sułek, Anna; Krysa, Wioletta; Stepniak, Iwona; Zieora-Jakutowicz, Karolina; Júlio, Filipa; Januário, Cristina; Coelho, Miguel; Mendes, Tiago; Valadas, Anabela; Andrade, Carlos; Gago, Miguel; Garrett, Carolina; Guerra, Maria Rosália; Lima, Joana; Massano, João; Meireles, Joana; Herrera, Carmen Durán; Garcia, Patrocinio Moreno; Barrero, Francisco; Morales, Blas; Cubo, Esther; Mariscal, Natividad; Sánchez, Jesús; Alonso-Frech, Fernando; Perez, Maria Rabasa; Fenollar, María; García, Rocío García-Ramos; Pin Quiroga, Purificacion; Vázquez Rivera, Susana; Villanueva, Clara; Alegre, Javier; Bascuñana, Mónica; Caldentey, Juan Garcia; Ventura, Marta Fatás; Ribas, Guillermo García; de Yébenes, Justo García; Moreno, José Luis López-Sendón; Ruíz, Pedro J García; Martínez-Descals, Asunción; Artiga, María José Saiz; Sánchez, Vicenta; Guerrero, Rosa; Bárcenas, Antonio Herranz; Perea, María Fuensanta Noguera; Fortuna, Lorenza; Torres, María Martirio Antequera; Reinante, Gema; Moreau, Laura Vivancos; Barbera, Miquel Aguilar; Guia, Dolors Badenes; Hernanz, Laura Casas; Catena, Judit López; Ferrer, Pilar Quiléz; Carruesco, Gemma Tome; Bas, Jordi; Busquets, Núria; Calopa, Matilde; Elorza, Marina Dalmau; López, Cristóbal Díez-Aja; Durán-Sindreu Terol, Santiago; Robert, Misericordia Floriach; Ruíz, Belén Garzón; Casado, Ana González; Martínez, Isabel Haro; Viladrich, Celia Mareca; Cárdenas, Regina Ponsi; Roca, Elvira; Llesoy, Joan Roig; Idiago, Jesús Miguel Ruiz; Vergara, Mar Ruíz; García, Socorro Soriano; Riballo, Antonio Villa; González, Sonia González; Guisasola, Luis Menéndez; Salvador, Carlos; Martín, Esther Suaréz San; González, Mónica; Gorospe, Aranzazú; Legarda, Inés; Arques, Penelope Navas; Rodríguez, María José Torres; Vives, Barbara; Gaston, Itziar; Martinez-Jaurrieta, Maria Dolores; Moreno, Jose Manuel Garcia; Peña, José Chacón; Avarvarei, Luminita Dinca; Bastida, Antonio Martín; Recio, Maria Fernández; Vergé, Luis Redondo; Sánchez, Violeta Sánchez; Carrillo, Fátima; Cáceres, María Teresa; Mir, Pablo; Suarez, María José Lama; Loutfi, Ghada; Olofsson, Carina; Stattin, Eva-Lena; Westman, Laila; Wikström, Birgitta; Pålhagen, Sven E; Paucar, Martin; Svenningsson, Per; Reza-Soltani, Tina Walldén; Höglund, Arja; Sandström, Britta; Høsterey-Ugander, Ulrika; Fredlund, Gunnel; Constantinescu, Radu; Neleborn-Lingefjärd, Liselotte; Stebler, Yanik; Kaelin, Alain; Romero, Irene; Schüpbach, Michael; Zaugg, Sabine Weber; Miedzybrodzka, Zosia; Rae, Daniela; Downie, Lorna; Simpson, Sheila; Summers, Fiona; Ure, Alexandra; Jack, Roisin; Matheson, Kirsty; Akhtar, Shahbana; Crooks, Jenny; Curtis, Adrienne; de Souza, Jenny; Rickards, Hugh; Wright, Jan; Barker, Roger A; O' Keefe, Deidre; Di Pietro, Anna; Fisher, Kate; Goodman, Anna; Hill, Susan; Mason, Sarah; Swain, Rachel; Guzman, Natalie Valle; Bisson, Jonathan; Busse, Monica; Butcher, Cynthia; Clenaghan, Catherine; Dunnett, Stephen; Handley, Olivia; Hunt, Sarah; Hughes, Alis; Johnstone, Catherine; Jones, Lesley; Jones, Una; Khalil, Hanan; Owen, Michael; Price, Kathleen; Rose, Linda Ellison; Rosser, Anne; Porteous, Mary; Edwards, Maureen; Ho, Carrie; McGill, Marie; Pearson, Pauline; Brockie, Peter; Foster, Jillian; Johns, Nicola; McKenzie, Sue; Rothery, Jean; Thomas, Gareth; Yates, Shona; Burrows, Liz; Fletcher, Amy; Harding, Alison; Laver, Fiona; Silva, Mark; Thomson, Aileen; Rowett, Liz; Gallantrae, Deena; Longthorpe, Mandy; Markova, Ivana; Raman, Ashok; Hamer, Stephanie; Yarduiman, Pam; Chu, Carol; Kraus, Alison; Wild, Sue; Musgrave, Hannah; Toscano, Jean; Jamieson, Stuart; Hobson, Emma; Clayton, Carole; Dipple, Heather; Middleton, Julia; Freire-Patino, Dawn; Andrews, Thomasin; Dougherty, Andrew; Kavalier, Fred; Golding, Charlotte; Laing, Hana; Lashwood, Alison; Robertson, Dene; Ruddy, Deborah; Whaite, Anna; Santhouse, Alastair; Patton, Michael; Peterson, Maria; Rose, Sarah; Bruno, Stefania; Chu, Elvina; Doherty, Karen; Haider, Salman; Hensman, Davina; Lahiri, Nayana; Lewis, Monica; Novak, Marianne; Patel, Aakta; Robertson, Nicola; Rosser, Elisabeth; Taylor, Rachel; Warner, Thomas; Wild, Edward; Craufurd, David; Howard, Liz; Sollom, Andrea; Snowden, Julie; Thompson, Jennifer; Jones, Mary; Murphy, Helen; Trender-Gerhard, Iris; Rogers, Dawn; Bek, Judith; Oughton, Emma; Johnson, Liz; Hare, Marianne; Arran, Natalie; Verstraelen, Nichola; Partington-Jones, Lucy; Huson, Susan; Stopford, Cheryl; Westmoreland, Leann; Davidson, Jill; Morgan, Karen; Savage, Lois; Singh, Baldev; Komati, Suresh; Nemeth, Andrea H; Armstrong, Richard; Valentine, Ruth; Siuda, Gill; Harrison, David; Hughes, Max; Parkinson, Andrew; Soltysiak, Beverley; Bandmann, Oliver; Bradbury, Alyson; Gill, Paul; Fairtlough, Helen; Fillingham, Kay; Foustanos, Isabella; Kazoka, Mbombe; O' Donovan, Kirsty; Taylor, Catherine; Tidswell, Katherine; Quarrell, Oliver
Source: Metzger, S, Walter, C, Riess, O, Nguyen, H P, Bachoud-Lévi, A-C, Bentivoglio, A R, Biunno, I, Bonelli, R M, Burgunder, J-M, Ferreira, J J, Heiberg, A, Illmann, T, Landwehrmeyer, G B, Levey, J, Ramos-Arroyo, M A, Nielsen, J, Koivisto, S P, Päivärinta, M, Roos, R A C, Sebastián, A R, Tabrizi, S, Vandenberghe, W, Verellen-Dumoulin, C, Zaremba, J, Uhrová, T, Wahlström, J, Barth, K, Correia-Guedes, L, Finisterra, A M, Garde, M B, Bos, R, Betz, S, Callaghan, J, Fullam, R, Ecker, D, Nielsen, M G, Hvalstedt, C, Held, C, Koppers, K, Laurà, M, Horta, S M, Descals, A M, ....
Publication Year: 2013
Collection: The University of Manchester: Research Explorer - Publications
Description: The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/23894380
DOI: 10.1371/journal.pone.0068951
Availability: https://research.manchester.ac.uk/en/publications/be3fc79e-f1f4-4ce1-a047-3156028d3d61; https://doi.org/10.1371/journal.pone.0068951
Rights: info:eu-repo/semantics/closedAccess
Accession Number: edsbas.9AB8C70F
Database: BASE