H63D HFE polymorphisms are associated with increased disease duration and decreased muscle superoxide dismutase-1 expression in amyotrophic lateral sclerosis patients

作者：Su Xiaowei W; Lee Sang Y; Mitchell Ryan M; Stephens Helen E; Simmons Zachary; Connor James R^*

来源：Muscle & Nerve, 2013, 48(2): 242-246.

DOI：10.1002/mus.23740

• amyotrophic lateral sclerosis
• H63D HFE polymorphism
• muscle biopsy
• neurodegenerative disorders
• SOD1

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.

• 出版日期2013-8