H63D HFE polymorphisms are associated with increased disease duration and decreased muscle superoxide dismutase-1 expression in amyotrophic lateral sclerosis patients.
INTRODUCTION
H63D HFE polymorphisms increase the risk of neurodegenerative disorders and, specifically, may increase amyotrophic lateral sclerosis (ALS) risk. Investigating the physiological alterations induced by H63D polymorphisms in ALS patients may elucidate mechanisms by which this genotype alters disease.


METHODS
Clinical measures and muscle biopsies were available from patients previously diagnosed with ALS who underwent HFE genotyping. Clinical outcomes and SOD1 protein expression were analyzed using standard statistical analyses.


RESULTS
ALS patients harboring H63D HFE (n = 16) had 28.1 months longer average disease duration and 39.3% lower muscle SOD1 protein than ALS patients with wild-type HFE (n = 22).


CONCLUSIONS
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. The association between HFE genotype and disease duration has important implications for clinical care and treatment trials.
['Su|Xiaowei W|XW|', 'Lee|Sang Y|SY|', 'Mitchell|Ryan M|RM|', 'Stephens|Helen E|HE|', 'Simmons|Zachary|Z|', 'Connor|James R|JR|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000690:Amyotrophic Lateral Sclerosis D005260:Female D005786:Gene Expression Regulation D056726:Genetic Association Studies D005838:Genotype D000071020:Hemochromatosis Protein D006639:Histidine D015395:Histocompatibility Antigens Class I D006801:Humans D008297:Male D008565:Membrane Proteins D008875:Middle Aged D018482:Muscle, Skeletal D010649:Phenylalanine D020641:Polymorphism, Single Nucleotide D013482:Superoxide Dismutase D000072105:Superoxide Dismutase-1
H63D HFE polymorphism amyotrophic lateral sclerosis neurodegenerative disorders muscle biopsy SOD1