H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis.
The H63D polymorphism in HFE has frequently been associated with susceptibility to amyotrophic lateral sclerosis (ALS). Regarding the role of HFE in iron homeostasis, iron accumulation is considered an important process in ALS. Furthermore, novel therapeutic strategies are being developed targeting this process. Evidence for this genetic association is, however, limited to several small studies. For this reason we studied the H63D polymorphism in a large European cohort including 3962 ALS patients and 5072 control subjects from 7 countries. After meta-analysis of previous studies and current findings we conclude that the H63D polymorphism in HFE is not associated with susceptibility to ALS, age at disease onset, or survival.
Department of Neurology, Rudolph Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
Wouter
W
van Rheenen
Frank P
FP
Diekstra
Perry T C
PT
van Doormaal
Meinie
M
Seelen
Kevin
K
Kenna
Russell
R
McLaughlin
Aleksey
A
Shatunov
David
D
Czell
Michael A
MA
van Es
Paul W J
PW
van Vught
Philip
P
van Damme
Bradley N
BN
Smith
Stefan
S
Waibel
H Jurgen
HJ
Schelhaas
Anneke J
AJ
van der Kooi
Marianne
M
de Visser
Markus
M
Weber
Wim
W
Robberecht
Orla
O
Hardiman
Pamela J
PJ
Shaw
Christopher E
CE
Shaw
Karen E
KE
Morrison
Ammar
A
Al-Chalabi
Peter M
PM
Andersen
Albert C
AC
Ludolph
Jan H
JH
Veldink
Leonard H
LH
van den Berg
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors
D005819:Genetic Markers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins