Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease

Kauwe, J. S. K., Bertelsen, S., Mayo, K., Cruchaga, C., Abraham, Richard Alun, Hollingworth, Paul, Harold, Denise ORCID: https://orcid.org/0000-0001-5195-0143, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259, Lovestone, S., Morris, J. C. and Goate, A. M. 2009. Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 153B (4) , pp. 955-959. 10.1002/ajmg.b.31053

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Abstract

Alzheimer's disease (AD) is a complex disease that is likely influenced by many genetic and environmental factors. Citing evidence that iron may play a role in AD pathology, Robson et al. [Robson et al. (2004); J Med Genet 41:261–265] reported that epistatic interaction between rs1049296 (P589S) in the transferrin gene (TF) and rs1800562 (C282Y) in the hemochromatosis gene (HFE) results in significant association with risk for AD. In this study we attempted to replicate their findings in a total of 1,166 cases and 1,404 controls from three European and European American populations. Allele and genotype frequencies were consistent across the three populations. Using synergy factor analysis (SFA) and Logistic Regression analysis we tested each population and the combined sample for interactions between these two SNPs and risk for AD. We observed significant association between bi-carriers of the minor alleles of rs1049296 and rs1800562 in the combined sample using SFA (P = 0.0016, synergy factor = 2.71) and adjusted SFA adjusting for age and presence of the APOE epsilon 4 allele (P  = 0.002, OR = 2.4). These results validate those of the previous report and support the hypothesis that iron transport and regulation play a role in AD pathology.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	transferrin; hemachromatosis gene; Alzheimer’s disease; epistasis; genetic association
Publisher:	Wiley-Blackwell
ISSN:	1552-4841
Last Modified:	19 Oct 2022 09:46
URI:	https://orca.cardiff.ac.uk/id/eprint/22146

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