HFE variants, APOE and Alzheimer's disease: Findings from the population-based Rotterdam Study

• Published in: Neurobiology of aging Vol. 30; no. 2; pp. 330 - 332
• Main Authors: Alizadeh, B.Z, Njajou, O.T, Millán, M.R, Hofman, A, Breteler, M.M, van Duijn, C.M
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01-02-2009; Elsevier
• Subjects: Age Distribution; Age of Onset; Aged; Aged, 80 and over; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer's disease; Apolipoproteins E - genetics; Biological and medical sciences; C282Y; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Development. Senescence. Regeneration. Transplantation; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genetic Variation - genetics; H63D; Hemochromatosis; Hemochromatosis Protein; HFE; Histocompatibility Antigens Class I - genetics; Humans; Incidence; Internal Medicine; Iron; Male; Medical sciences; Membrane Proteins - genetics; Middle Aged; Netherlands - epidemiology; Neurology; Polymorphism, Single Nucleotide - genetics; Risk Assessment - methods; Risk Factors; Vertebrates: nervous system and sense organs; Iron; Hemochromatosis; Alzheimer's disease; HFE; H63D; C282Y; Nervous system diseases; Senescence; Alzheimer disease; Cerebral disorder; Apolipoprotein E; Central nervous system disease; Degenerative disease
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2007.05.026

Abstract Iron is a reactive oxygen species and has been implicated in the pathogenesis of Alzheimer's disease (AD). In a population-based cohort study, including 268 incident AD patients and 2079 control individuals, we investigated the influence of the HFE C282Y and H63D variants and the apolipoprotein E4 ( APOEε4 ) allele on the incidence, and age at onset of AD. There was no significant difference in the frequency of HFE variants in AD patients compared to controls. There was no significant effect modification by the APOEε4 allele. The mean age at onset was earlier in H63D homozygotes compared to non-carriers of this variant, in men (76.9 ± 3.2 compared to 82.2 ± 1.7) and women (82.1 ± 3.9 compared to 84.5 ± 1.7). In addition, in APOEε4 carriers, the mean age at onset of AD was earlier in men homozygous for the H63D variant (73.2 ± 2.1 versus 78.7 ± 1.6, p = 0.05). Our results suggest that HFE variants are not strong determinants of AD in the general population but may modify the age of onset.