Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project
Neurobiology of Aging: age-related phenomena, neurodegeneration and neuropathology , Volume 33 - Issue 1
Iron overload may contribute to the risk of Alzheimer's disease (AD). In the Epistasis Project, with 1757 cases of AD and 6295 controls, we studied 4 variants in 2 genes of iron metabolism: hemochromatosis (HFE) C282Y and H63D, and transferrin (TF) C2 and -2G/A. We replicated the reported interaction between HFE 282Y and TF C2 in the risk of AD: synergy factor, 1.75 (95% confidence interval, 1.1-2.8, p = 0.02) in Northern Europeans. The synergy factor was 3.1 (1.4-6.9; 0.007) in subjects with the APOEε4 allele. We found another interaction, between HFE 63HH and TF -2AA, markedly modified by age. Both interactions were found mainly or only in Northern Europeans. The interaction between HFE 282Y and TF C2 has now been replicated twice, in altogether 2313 cases of AD and 7065 controls, and has also been associated with increased iron load. We therefore suggest that iron overload may be a causative factor in the development of AD. Treatment for iron overload might thus be protective in some cases.
|Apolipoprotein E ε4, Glycosylation, Iron chelation, Microglia, Mild cognitive impairment, Neurodegeneration, Onset age, Transferrin saturation|
|Neurobiology of Aging: age-related phenomena, neurodegeneration and neuropathology|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Lehmann, D.J, Schuur, M, Warden, D.R, Hammond, N, Belbin, O, Kölsch, H, … Alvarez, V. (2012). Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project. Neurobiology of Aging: age-related phenomena, neurodegeneration and neuropathology, 33(1). doi:10.1016/j.neurobiolaging.2010.07.018