• Online Features  This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (27)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurology  • Amyotrophic Lateral Sclerosis  • Neurogenetics  • Neuromuscular diseases  • Neurology, Other  • Genetic Disorders  • Genetics, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

Nadia A. Sutedja, MD; Richard J. Sinke, PhD; Paul W. J. Van Vught, MSc; Michiel W. Van der Linden, MD, PhD; John H. J. Wokke, MD, PhD; Cornelia M. Van Duijn, PhD; Omer T. Njajou, DSc, PhD; Yvonne T. Van der Schouw, PhD; Jan H. Veldink, MD, PhD; Leonard H. Van den Berg, MD, PhD

Arch Neurol. 2007;64(1):63-67.

Background  Mutations in HFE, a gene defect that can disrupt iron metabolism, have been implicated in increasing the risk of developing amyotrophic lateral sclerosis (ALS).

Objective  To further establish the association between ALS and HFE mutations by investigating whether HFE mutations are associated with an increased risk of developing ALS in a population in the Netherlands and by pooling our results with those from previous studies.

Design  Retrospective study.

Setting  Tertiary referral center for neuromuscular disorders.

Participants  Genotyping for 2 common HFE mutations was performed in 289 patients with ALS and 5886 population-based controls in the Netherlands between January 1, 2000, and December 31, 2004.

Main Outcome Measures  Development of ALS and clinical phenotype were compared among the different HFE genotypes, adjusting for known prognostic factors such as age at onset and sex.

Results  Homozygosity for H63D was associated with an increased risk of developing ALS (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.1- 4.1). After pooling our results with those from previous studies, a positive association between H63D homozygotes (OR, 2.7; 95% CI, 1.7-4.4), heterozygotes (OR, 1.5; 95% CI, 1.0-2.1), and mutation carriers (OR, 1.7; 95% CI, 1.1-2.5) was found. Within the patient group, heterozygosity for the H63D mutation was associated with a higher age at onset.

Conclusions  These findings suggest that H63D mutations in HFE play a role in the pathogenesis of ALS in various populations. This association might involve a later-onset subset of ALS.

Author Affiliations: Departments of Neurology (Drs Sutedja, Van Vught, Wokke, Veldink, and Van den Berg) and Medical Genetics (Dr Sinke) and Julius Center for Health Sciences and Primary Care (Drs Van der Linden and Van der Schouw), University Medical Center Utrecht, Utrecht, and Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam (Drs Van Duijn and Njajou), the Netherlands.

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Mutant HFE H63D Protein Is Associated with Prolonged Endoplasmic Reticulum Stress and Increased Neuronal Vulnerability
Liu et al.
J. Biol. Chem. 2011;286:13161-13170.
ABSTRACT | FULL TEXT  

HFE Gene Variants Affect Iron in the Brain
Nandar and Connor
J. Nutr. 2011;141:729S-739S.
ABSTRACT | FULL TEXT  

Trends and determinants of end-of-life practices in ALS in the Netherlands
Maessen et al.
Neurology 2009;73:954-961.
ABSTRACT | FULL TEXT  

A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis
Mitchell et al.
Neurology 2009;72:14-19.
ABSTRACT | FULL TEXT  

Genetics of sporadic amyotrophic lateral sclerosis
Schymick et al.
Hum Mol Genet 2007;16:R233-R242.
ABSTRACT | FULL TEXT