title: Evaluation of HFE (hemochromatosis) mutations as genetic modifiers in sporadic AD and MCI.
abstract: BACKGROUND
  Pathological brain iron deposition has been implicated as a source of neurotoxic reactive oxygen species in Alzheimer disease (AD). Recent reports suggest that heterozygosity for the two common hfe mutations responsible for hereditary hemochromatosis (HH) may be a risk factor for AD, possibly by accelerating brain iron accumulation.
  
  
  METHODS
  To test this hypothesis, we genotyped 213 sporadic AD, 106 MCI, and 63 normal elderly control (NEC) individuals for the H63D and C282Y hfe mutations by polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) analysis. We determined the relationship of these mutations to the demographic, clinical, and neuropsychological features of AD and MCI, and evaluated whether an interaction existed between hfe and apolipoprotein E (apoE) status in these patients.
  
  
  RESULTS
  We observed no significant impact of H63D or C282Y heterozygosity on age at AD symptoms onset or diagnosis, age at onset of cognitive symptoms (AD and MCI combined), rates of MCI-to-AD conversion or specific neuropsychological deficits. No interactions between hfe zygosity and apoE status were discerned. Patients homozygous for H63D exhibited trends towards accelerated MCI-to-AD conversion rates and a subset of younger individuals (aged 55-75) exhibited earlier onset of cognitive symptoms relative to wild-type hfe and H63D heterozygotes.
  
  
  CONCLUSIONS
  Contrary to earlier reports, the results of the present study do not implicate the common hfe mutations as genetic modifiers of sporadic AD and MCI. Trends towards accelerated cognitive dysfunction in H63D homozygotes warrant further study.
authors.affiliation: Blomfield Centre for Research in Aging, Montreal, Que., Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Berlin
authors.forename: George
authors.initials: G
authors.lastname: Chong
authors.forename: Howard
authors.initials: H
authors.lastname: Chertkow
authors.forename: Howard
authors.initials: H
authors.lastname: Bergman
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Phillips
authors.forename: Hyman M
authors.initials: HM
authors.lastname: Schipper
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000523:psychology; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000235:genetics* / Q000523:psychology; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests / Q000706:statistics & numerical data
chemical_list: D005819:Genetic Markers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins