RT Journal
A1 Sutedja NA, Sinke RJ, Van Vught PJ, et al
T1 THe association between h63d mutations in hfe and amyotrophic lateral sclerosis in a dutch population
JF Archives of Neurology
JO Archives of Neurology
YR 2007
FD January 1
VO 64
IS 1
SP 63
OP 67
DO 10.1001/archneur.64.1.63
UL http://dx.doi.org/10.1001/archneur.64.1.63
AB 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.