HFE p.H63D polymorphism does not influence ALS phenotype and survival

Adriano Chiò; Gabriele Mora; Mario Sabatelli; Claudia Caponnetto; Christian Lunetta; Bryan J Traynor; Janel O Johnson; Mike A Nalls; Andrea Calvo; Cristina Moglia; Giuseppe Borghero; Maria Rosaria Monsurrò; Vincenzo La Bella; Paolo Volanti; Isabella Simone; Fabrizio Salvi; Francesco O Logullo; Riva Nilo; Fabio Giannini; Jessica Mandrioli; Raffaella Tanel; Maria Rita Murru; Paola Mandich; Marcella Zollino; Francesca L Conforti; Silvana Penco; ITALSGEN consortium; SARDINIALS consortium; Maura Brunetti; Marco Barberis; Gabriella Restagno

doi:10.1016/j.neurobiolaging.2015.06.016

HFE p.H63D polymorphism does not influence ALS phenotype and survival

Neurobiol Aging. 2015 Oct;36(10):2906.e7-11. doi: 10.1016/j.neurobiolaging.2015.06.016. Epub 2015 Jun 18.

Authors

Adriano Chiò¹, Gabriele Mora², Mario Sabatelli³, Claudia Caponnetto⁴, Christian Lunetta⁵, Bryan J Traynor⁶, Janel O Johnson⁷, Mike A Nalls⁸, Andrea Calvo⁹, Cristina Moglia¹⁰, Giuseppe Borghero¹¹, Maria Rosaria Monsurrò¹², Vincenzo La Bella¹³, Paolo Volanti¹⁴, Isabella Simone¹⁵, Fabrizio Salvi¹⁶, Francesco O Logullo¹⁷, Riva Nilo¹⁸, Fabio Giannini¹⁹, Jessica Mandrioli²⁰, Raffaella Tanel²¹, Maria Rita Murru²², Paola Mandich⁴, Marcella Zollino²³, Francesca L Conforti²⁴, Silvana Penco²⁵; ITALSGEN consortium; SARDINIALS consortium; Maura Brunetti²⁶, Marco Barberis²⁶, Gabriella Restagno²⁷

Collaborators

Isabella Simone, Giancarlo Logroscino, Ilaria Bartolomei, Margherita Capasso, Gianluigi Mancardi, Paola Origone, Kalliopi Marinou, Riccardo Sideri, Lorena Mosca, Giuseppe Lauria Pinter, Massimo Corbo, Nicola Fini, Eleni Georgoulopoulou, Lucio Tremolizzo, Gioacchino Tedeschi, Francesca Trojsi, Giovanni Piccirillo, Viviana Cristillo, Vincenzo la Bella, Rossella Spataro, Tiziana Colletti, Amelia Conte, Marco Luigetti, Serena Lattante, Giuseppe Marangi, Marialuisa Santarelli, Antonio Petrucci, Stefania Battistini, Claudia Ricci, Michele Benigni, Federico Casale, Giuseppe Marrali, Giuseppe Fuda, Irene Ossola, Stefania Cammarosano, Antonio Ilardi, Davide Bertuzzo, Raffaella Tanel, Fabrizio Pisano, Emanuela Costantino, Carla Pani, Roberta Puddu, Carla Caredda, Valeria Piras, Stefania Tranquilli, Stefania Cuccu, Daniela Corongiu, Maurizio Melis, Antonio Milia, Francesco Marrosu, Maria Giovanna Marrosu, Gianluca Floris, Antonino Cannas, Stefania Cuccu, Stefania Tranquilli, Anna Ticca, Maura Pugliatti, Angelo Pirisi, Leslie D Parish, Patrizia Occhineri, Enzo Ortu, Tea B Cau, Daniela Loi

Affiliations

¹ ALS Center, "Rita Levi Montalcini" Department of Neuroscience, Neurology II, University of Torino, Torino, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy. Electronic address: [email protected].
² Department of Neurological Rehabilitation, Fondazione Salvatore Maugeri, IRCCS, Istituto Scientifico di Milano, Milan, Italy.
³ Neurological Institute, Catholic University and I.C.O.M.M. Association for ALS Research, Rome, Italy.
⁴ Department of Neurosciences, Ophthalmology, Genetics, Rehabilitation and Child Health, IRCCS Azienda Ospedaliero-Universitaria San Martino IST, University of Genoa, Genoa, Italy.
⁵ NEuroMuscular Omnicenter, Serena Onlus Foundation, Milan, Italy.
⁶ Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁷ Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA; Department of Neurology, Neurological Institute, Neuromuscular Center, Cleveland Clinic, Cleveland, OH, USA.
⁸ Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁹ ALS Center, "Rita Levi Montalcini" Department of Neuroscience, Neurology II, University of Torino, Torino, Italy; Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.
¹⁰ ALS Center, "Rita Levi Montalcini" Department of Neuroscience, Neurology II, University of Torino, Torino, Italy.
¹¹ Department of Neurology, Azienda Universitario Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy.
¹² Department of Neurological Sciences, Second University of Naples, Naples, Italy.
¹³ ALS Clinical Research Center, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy.
¹⁴ Neurorehabilitation Unit/ALS Center, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Mistretta, Mistretta, Italy.
¹⁵ Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.
¹⁶ Center for Diagnosis and Cure of Rare Diseases, Department of Neurology, IRCCS Institute of Neurological Sciences, Bologna, Italy.
¹⁷ Neurological Clinic, Marche Polytechnic University, Ancona, Italy.
¹⁸ Department of Neurology and Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁹ Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
²⁰ Department of Neuroscience, S. Agostino- Estense Hospital, University of Modena and Reggio Emilia, Modena, Italy.
²¹ Department of Neurology, Santa Chiara Hospital, Trento, Italy.
²² Multiple Sclerosis Centre, ASL 8, Cagliari/Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy.
²³ Institute of Medical Genetics, Catholic University of Sacred Heart, Rome, Italy.
²⁴ Institute of Neurological Sciences, National Research Council, Mangone, Cosenza, Italy.
²⁵ Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
²⁶ ALS Center, "Rita Levi Montalcini" Department of Neuroscience, Neurology II, University of Torino, Torino, Italy; Laboratory of Molecular Genetics, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.
²⁷ Laboratory of Molecular Genetics, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.

PMID: 26174855
PMCID: PMC5183653
DOI: 10.1016/j.neurobiolaging.2015.06.016

Abstract

It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression both in the SOD1 transgenic mouse and in amyotrophic lateral sclerosis (ALS) patients. We have evaluated the effect of HFE p.His63Asp polymorphism on the phenotype in 1351 Italian ALS patients (232 of Sardinian ancestry). Patients were genotyped for the HFE p.His63Asp polymorphism (CC, GC, and GG). All patients were also assessed for C9ORF72, TARDBP, SOD1, and FUS mutations. Of the 1351 ALS patients, 363 (29.2%) were heterozygous (GC) for the p.His63Asp polymorphism and 30 (2.2%) were homozygous for the minor allele (GG). Patients with CC, GC, and GG polymorphisms did not significantly differ by age at onset, site of onset of symptoms, and survival; however, in SOD1 patients with CG or GG polymorphism had a significantly longer survival than those with a CC polymorphism. Differently from what observed in the mouse model of ALS, the HFE p.His63Asp polymorphism has no effect on ALS phenotype in this large series of Italian ALS patients.

Keywords: Amyotrophic lateral sclerosis; HFE polymorphisms; SOD1; phenotype; survival.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alleles
Amyotrophic Lateral Sclerosis / genetics*
Amyotrophic Lateral Sclerosis / mortality*
Animals
Disease Progression
Female
Genetic Association Studies*
Hemochromatosis Protein
Histocompatibility Antigens Class I / genetics*
Humans
Italy / epidemiology
Male
Membrane Proteins / genetics*
Mice
Middle Aged
Phenotype*
Polymorphism, Genetic / genetics*
Superoxide Dismutase / genetics
Superoxide Dismutase-1
Survival Rate

Substances

HFE protein, human
Hemochromatosis Protein
Histocompatibility Antigens Class I
Membrane Proteins
SOD1 protein, human
Sod1 protein, mouse
Superoxide Dismutase
Superoxide Dismutase-1

Abstract

Publication types

MeSH terms

Substances

Grants and funding