title: HFE p.H63D polymorphism does not influence ALS phenotype and survival.
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.
authors.affiliation: 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: achio@usa.net.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.affiliation: Department of Neurological Rehabilitation, Fondazione Salvatore Maugeri, IRCCS, Istituto Scientifico di Milano, Milan, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
authors.affiliation: Neurological Institute, Catholic University and I.C.O.M.M. Association for ALS Research, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Sabatelli
authors.affiliation: Department of Neurosciences, Ophthalmology, Genetics, Rehabilitation and Child Health, IRCCS Azienda Ospedaliero-Universitaria San Martino IST, University of Genoa, Genoa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Caponnetto
authors.affiliation: NEuroMuscular Omnicenter, Serena Onlus Foundation, Milan, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Lunetta
authors.affiliation: Neuromuscular Diseases Research Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.affiliation: 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.
authors.forename: Janel O
authors.initials: JO
authors.lastname: Johnson
authors.affiliation: Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mike A
authors.initials: MA
authors.lastname: Nalls
authors.affiliation: 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.affiliation: ALS Center, "Rita Levi Montalcini" Department of Neuroscience, Neurology II, University of Torino, Torino, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Moglia
authors.affiliation: Department of Neurology, Azienda Universitario Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borghero
authors.affiliation: Department of Neurological Sciences, Second University of Naples, Naples, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Monsurrò
authors.affiliation: ALS Clinical Research Center, Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: La Bella
authors.affiliation: Neurorehabilitation Unit/ALS Center, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Mistretta, Mistretta, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Volanti
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Simone
authors.affiliation: Center for Diagnosis and Cure of Rare Diseases, Department of Neurology, IRCCS Institute of Neurological Sciences, Bologna, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salvi
authors.affiliation: Neurological Clinic, Marche Polytechnic University, Ancona, Italy.
authors.forename: Francesco O
authors.initials: FO
authors.lastname: Logullo
authors.affiliation: Department of Neurology and Institute of Experimental Neurology (INSPE), IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Riva
authors.initials: R
authors.lastname: Nilo
authors.affiliation: Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Giannini
authors.affiliation: Department of Neuroscience, S. Agostino- Estense Hospital, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Mandrioli
authors.affiliation: Department of Neurology, Santa Chiara Hospital, Trento, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Tanel
authors.affiliation: Multiple Sclerosis Centre, ASL 8, Cagliari/Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Murru
authors.affiliation: Department of Neurosciences, Ophthalmology, Genetics, Rehabilitation and Child Health, IRCCS Azienda Ospedaliero-Universitaria San Martino IST, University of Genoa, Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Mandich
authors.affiliation: Institute of Medical Genetics, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Zollino
authors.affiliation: Institute of Neurological Sciences, National Research Council, Mangone, Cosenza, Italy.
authors.forename: Francesca L
authors.initials: FL
authors.lastname: Conforti
authors.affiliation: Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Penco
authors.affiliation: 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.
authors.forename: Maura
authors.initials: M
authors.lastname: Brunetti
authors.affiliation: 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.
authors.forename: Marco
authors.initials: M
authors.lastname: Barberis
authors.affiliation: Laboratory of Molecular Genetics, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Torino, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Restagno
mesh_terms: D000368:Aged; D000483:Alleles; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000401:mortality*; D000818:Animals; D018450:Disease Progression; D005260:Female; D056726:Genetic Association Studies; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D015996:Survival Rate
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis; HFE polymorphisms; SOD1; phenotype; survival