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

Xiaowei W. Su, Sang Lee, Ryan M. Mitchell, Helen E. Stephens, Zachary Simmons, James Connor

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)242-246
Number of pages5
JournalMuscle and Nerve
Volume48
Issue number2
DOIs
StatePublished - Aug 1 2013

Fingerprint

Amyotrophic Lateral Sclerosis
Muscles
Genotype
Muscle Proteins
Superoxide Dismutase-1
Neurodegenerative Diseases
Biopsy

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

Cite this

@article{13af5b1f602c44bcbbe63d86fd854a1e,
title = "H63D HFE polymorphisms are associated with increased disease duration and decreased muscle superoxide dismutase-1 expression in amyotrophic lateral sclerosis patients",
abstract = "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.",
author = "Su, {Xiaowei W.} and Sang Lee and Mitchell, {Ryan M.} and Stephens, {Helen E.} and Zachary Simmons and James Connor",
year = "2013",
month = "8",
day = "1",
doi = "10.1002/mus.23740",
language = "English (US)",
volume = "48",
pages = "242--246",
journal = "Muscle and Nerve",
issn = "0148-639X",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

H63D HFE polymorphisms are associated with increased disease duration and decreased muscle superoxide dismutase-1 expression in amyotrophic lateral sclerosis patients. / Su, Xiaowei W.; Lee, Sang; Mitchell, Ryan M.; Stephens, Helen E.; Simmons, Zachary; Connor, James.

In: Muscle and Nerve, Vol. 48, No. 2, 01.08.2013, p. 242-246.

Research output: Contribution to journalArticle

TY - JOUR

T1 - H63D HFE polymorphisms are associated with increased disease duration and decreased muscle superoxide dismutase-1 expression in amyotrophic lateral sclerosis patients

AU - Su, Xiaowei W.

AU - Lee, Sang

AU - Mitchell, Ryan M.

AU - Stephens, Helen E.

AU - Simmons, Zachary

AU - Connor, James

PY - 2013/8/1

Y1 - 2013/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84881025084&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881025084&partnerID=8YFLogxK

U2 - 10.1002/mus.23740

DO - 10.1002/mus.23740

M3 - Article

C2 - 23813494

AN - SCOPUS:84881025084

VL - 48

SP - 242

EP - 246

JO - Muscle and Nerve

JF - Muscle and Nerve

SN - 0148-639X

IS - 2

ER -