Because the H63D HFE polymorphism is present in 30% of patients with ALS, studying disease progression in patients who receive statins, stratified for HFE genotype, may guide therapy.
In particular, human haemochromatosis protein (HFE) is involved in iron metabolism, and HFE H63D polymorphism has been related to the risk of amyotrophic lateral sclerosis and Alzheimer's disease.
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.
After meta-analysis of previous studies and current findings we conclude that the H63D polymorphism in HFE is not associated with susceptibility to ALS, age at disease onset, or survival.
Combined with previous reports suggesting the H63D polymorphism is associated with ALS, these results support a model wherein the H63D polymorphism is involved in ALS by means of pathways involving SOD1 but may limit cellular damage in individuals who develop disease.
A specific polymorphism in the hemochromatosis (HFE) gene, H63D, is over-represented in neurodegenerative disorders such as amyotrophic lateral sclerosis and Alzheimer disease.