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

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

Adriano Chiò  1 , Gabriele Mora  2 , Mario Sabatelli  3 , Claudia Caponnetto  4 , Christian Lunetta  5 , Bryan J Traynor  6 , Janel O Johnson  7 , Mike A Nalls  8 , Andrea Calvo  9 , Cristina Moglia  10 , Giuseppe Borghero  11 , Maria Rosaria Monsurrò  12 , Vincenzo La Bella  13 , Paolo Volanti  14 , Isabella Simone  15 , Fabrizio Salvi  16 , Francesco O Logullo  17 , Riva Nilo  18 , Fabio Giannini  19 , Jessica Mandrioli  20 , Raffaella Tanel  21 , Maria Rita Murru  22 , Paola Mandich  4 , Marcella Zollino  23 , Francesca L Conforti  24 , Silvana Penco  25 ; ITALSGEN consortium; SARDINIALS consortium; Maura Brunetti  26 , Marco Barberis  26 , Gabriella Restagno  27
Collaborators, Affiliations

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

Adriano Chiò et al. Neurobiol Aging. 2015 Oct.

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.

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Conflict of interest statement

statement The authors have no actual or potential conflicts of interest.

Figures

Fig. 1
Fig. 1. Italian patients
Survival curves by HFE genotype. CC, median survival time 3.0 years (interquartile range 1.9–5.5); GC/GG, median survival time 3.4 years (interquartile range 2.0–6.7). p = n.s. CC, blue; GC/GG green.
Fig. 2
Fig. 2. Sardinian patients
Survival curves by HFE genotype. CC, median survival time 4.7 years (interquartile range 2.4–14.2); GC/GG, median survival time 3.5 years (interquartile range 2.3–10.3). p = n.s. CC, blue; GC/GG green.
Fig. 3
Fig. 3. Italian patients carrying SOD1 mutations
CC, median survival time 2.1 years (interquartile range 2.6–8.4); GC/GG, median survival time 15.3 years (interquartile range 1.2–15.3). p = 0.04. CC, blue; GC/GG green.
See this image and copyright information in PMC

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