The hemochromatosis gene affects the age of onset of sporadic Alzheimer’s disease

Abstract

NEUROBIOL AGING. In the present study we analysed the genotype of HFE, the gene involved in hemochromatosis, in 107 patients with sporadic late-onset AD and in 99 age-matched non-demented controls. We observed that patients carrying the mutant HFE-H63D allele had a mean age at onset of 71.7 Ϯ 6.0 years versus 76.6 Ϯ 5.8 years of those who were homozygous for the wild-type allele (p ϭ 0.001). The frequency of the HFE-H63D mutation was highest (0.22) in the patients aged Ͻ70 years at the time of disease onset, whereas it was 0.12 in those with disease onset at an age of 70 -80 years, and 0.04 in those aged more than 80 years. The APOE genotype did not significantly modify the effect of HFE on age at onset. We conclude that mild disturbances of iron homeostasis associated with a common genetic determinant may interact with other pathogenic mechanisms involved in AD. HFE mutations may anticipate AD clinical presentation in susceptible individuals.

Gender and Iron Genes May Modify Associations Between Brain Iron and Memory in Healthy Aging

“…We also observed that gene variants involved in iron metabolism (hemochromatosis H63D (HFE H63D) and transferrin C2 (TfC2) variants) are associated with higher brain iron levels in healthy older men (Bartzokis et al, 2010). These two gene variants are highly prevalent (affecting approximately 50% of the population), and some studies have shown an association of these variants with higher risk of developing AD (Connor and Lee, 2006;Lehmann et al, 2010;Sampietro et al, 2001;Moalem et al, 2000). We therefore examined memory function in the context of gender and the presence (IRON + ) or absence (IRONÀ) of these iron gene variants.…”

Association between the MHC class I gene HFE polymorphisms and longevity: a study in Sicilian population

“…Thus, it seems that H63D mutations may anticipate sporadic late-onset AD clinical presentation in susceptible individuals. 33 In another study, in patients with familial AD (FAD) C282Y and H63D mutations were over-represented in men and under-represented in women with FAD. 34 Thus, the possibility that HFE mutations are important new genetic risk factors for AD should be pursued further.…”

Candidate Gene Association Studies in Sporadic Alzheimer’s Disease

“…Two common missense HFE gene mutations have been associated with hemochromatosis (C228Y and H63D). The age at onset of AD patients carrying one or two copies of the mutant HFE-H63D allele was an average of 5 years less than that of AD patients homozygous for the HFE-H63D wild-type allele [104]. Therefore, HFE mutations may anticipate the clinical presentation of AD in susceptible individuals.…”