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.
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.
Authors: Adriano Chiò; Gabriele Mora; Mario Sabatelli; Claudia Caponnetto; Christian Lunetta; Bryan J Traynor; Janel O Johnson; Mike A Nalls; Andrea Calvo; Cristina Moglia; Giuseppe Borghero; Maria Rosaria Monsurrò; Vincenzo La Bella; Paolo Volanti; Isabella Simone; Fabrizio Salvi; Francesco O Logullo; Riva Nilo; Fabio Giannini; Jessica Mandrioli; Raffaella Tanel; Maria Rita Murru; Paola Mandich; Marcella Zollino; Francesca L Conforti; Silvana Penco; Maura Brunetti; Marco Barberis; Gabriella Restagno Journal: Neurobiol Aging Date: 2015-06-18 Impact factor: 4.673
Authors: Ki-Do Eum; Ryan M Seals; Kathryn M Taylor; Matthew Grespin; David M Umbach; Howard Hu; Dale P Sandler; Freya Kamel; Marc G Weisskopf Journal: Amyotroph Lateral Scler Frontotemporal Degener Date: 2014-10-08 Impact factor: 4.092
Authors: Silke Schmidt; Kelli D Allen; Valerie T Loiacono; Barbara Norman; Catherine L Stanwyck; Kristina M Nord; Christina D Williams; Edward J Kasarskis; Freya Kamel; Valerie McGuire; Lorene M Nelson; Eugene Z Oddone Journal: Neuroepidemiology Date: 2008-04-18 Impact factor: 3.282