HFE p.His63Asp polymorphism is not a modifier of ALS phenotype (P2.049)

OBJECTIVE: To evaluate the effect of HFE p.His63Asp polymorphism on the phenotype of a large series of Italian ALS patients. BACKGROUND: It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression in animal models of ALS (Nandar et al, Biochim Biophys Acta This finding was replicated in 35 ALS patients (Su et al, Muscle Nerve 2014). DESIGN/METHODS: A total of 1333 Italian ALS patients (234 of Sardinian ancestry) were genotyped for the p.His63Asp polymorphism of the HFE gene. Patients with other gene polymorphisms were excluded. All patients were also assessed for C9ORF72, TARDBP, SOD1 and FUS mutations. Patients’ survival and clinical phenotype were compared to the HFE RESULTS: Of the 1136 ALS patients, 389 (29.2[percnt]) were heterozygous for the p.His63Asp polymorphism. The following mutations of major ALS genes were found: TARDBP, 75; C9ORF72, 72; SOD1, 26, FUS 14. Patients with and without HFE polymorphism did not significantly differ for age at onset (61.9 [SD 11.4] vs 62.0 [SD 11.9] years, p= n.s.) or site of onset of symptoms (bulbar onset, 25.8[percnt] vs. 25.7[percnt], p=n.s.) Survival from symptom onset was also similar in the two group of patients (p.His63Asp carries, median survival time 3.4 years, interquartile range [IQR] 2.1-6.7; non-carriers, 3.2 years, IQR 1.9-6.1]). These findings did not change when excluding patients with major gene mutations or when evaluating separately patients from continental Italy and Sardinia. CONCLUSIONS: 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. Study Supported by: Ministero della Salute (grant RF-2010-2309849), European Community’s Health Seventh Framework Programme (grant agreement 259867), ARISLA (SARDINIALS project) and Joint Programme - Neurodegenerative Disease Research (Italian Ministry of Education and University) (Sophia and Strength projects). Disclosure: Dr. Mora has nothing to disclose. Dr. Barberis has nothing to disclose. Dr. Restagno has nothing to disclose. Dr. Brunetti has nothing to disclose. Dr. Sabatelli has nothing to disclose. Dr. Zollino has nothing to disclose. Dr. Battistini has nothing to disclose. Dr. Conforti has nothing to disclose. Dr. Caponnetto has nothing to disclose. Dr. Mandich has nothing to disclose. Dr. Mandrioli has nothing to disclose. Dr. Penco has nothing to disclose. Dr. Lunetta has nothing to disclose. Dr. Borghero has nothing to disclose. Dr. Murru has nothing to disclose. Dr. Monsurro has nothing to disclose. Dr. Tedeschi has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, Bayer Schering Pharma, Novartis, and Biogen Idec as a speaker. Dr. Volanti has nothing to disclose. Dr. Simone has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc., and Biogen Idec. Dr. Logroscino has received personal compensation for activities with Novartis, GlaxoSmithKline, and Boerhinger, and as a member of the Cohorts Project in Biomedicine. Dr. Logroscino has received personal compensation in an editorial capacity for Karger. Dr. Logullo has nothing to disclose. Dr. Salvi has received research support from the Fondazione Hilarescere. Dr. Riva has nothing to disclose. controls funded by Merck Inc., $1,300,000. Dr. Calvo has nothing to disclose. Adriano Chio serves on a scientific advisory board for Biogen Idec, Cytokinetics and Italfamaco,