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<i>Background</i>: Data from published studies about the effect of HFE polymorphisms on ALS risk, phenotype, and survival are still inconclusive. We aimed at evaluating whether the p.H63D polymorphism is a modifier of phenotype and survival in <i>SOD1</i>-mutated patients. <i>Methods</i>: We included 183 <i>SOD1</i>-mutated ALS patients. Mutations were classified as severe or mild according to the median survival of the study population. Patients were screened for the <i>HFE</i> p.H63D polymorphism. Survival was calculated using the Kaplan–Meier modeling, and differences were measured by the log-rank test. Multivariable analysis was performed with the Cox proportional hazards model (stepwise backward). <i>Results</i>: <i>SOD1</i> severe mutation carriers show more frequent familial history for ALS and shorter survival compared to mild mutation carriers. Carriers and non-carriers of the p.H63D polymorphism did not differ in terms of sex ratio, frequency of positive familial history, age at onset, and bulbar/spinal ratio. In univariate and in Cox multivariable analysis using sex, age at onset, site of onset, family history, country of origin, and mutation severity as covariates, p.H63D carriers had a longer survival (<i>p</i> = 0.034 and <i>p</i> = 0.004). <i>Conclusions</i>: We found that <i>SOD1</i>-mutated ALS patients carrying the p.H63D HFE polymorphism have a longer survival compared to non-carriers, independently of sex, age and site of onset, family history, nation of origin, and severity of mutations, suggesting a possible role as disease progression modifier for the p.H63D <i>HFE</i> polymorphism in <i>SOD1</i>-ALS.