Transferrin and HFE genes interact in Alzheimer's disease risk: The Epistasis Project
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 inter...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1826302648971689984 |
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| author | Lehmann, D Schuur, M Warden, DR Hammond, N Belbin, O Kölsch, H Lehmann, MG Wilcock, G Brown, K Kehoe, P Morris, C Barker, R Coto, E Alvarez, V Deloukas, P Mateo, I Gwilliam, R Combarros, O Arias-Vásquez, A Aulchenko, Y Ikram, M Breteler, M van Duijn, C Oulhaj, A Heun, R |
| author_facet | Lehmann, D Schuur, M Warden, DR Hammond, N Belbin, O Kölsch, H Lehmann, MG Wilcock, G Brown, K Kehoe, P Morris, C Barker, R Coto, E Alvarez, V Deloukas, P Mateo, I Gwilliam, R Combarros, O Arias-Vásquez, A Aulchenko, Y Ikram, M Breteler, M van Duijn, C Oulhaj, A Heun, R |
| author_sort | Lehmann, D |
| collection | OXFORD |
| description | 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. © 2012 Elsevier Inc. |
| first_indexed | 2024-03-07T05:50:47Z |
| format | Journal article |
| id | oxford-uuid:e8d0674a-7e1a-4fed-bbf4-aea3a0eef99c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:50:47Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:e8d0674a-7e1a-4fed-bbf4-aea3a0eef99c2022-03-27T10:49:33ZTransferrin and HFE genes interact in Alzheimer's disease risk: The Epistasis ProjectJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e8d0674a-7e1a-4fed-bbf4-aea3a0eef99cEnglishSymplectic Elements at Oxford2012Lehmann, DSchuur, MWarden, DRHammond, NBelbin, OKölsch, HLehmann, MGWilcock, GBrown, KKehoe, PMorris, CBarker, RCoto, EAlvarez, VDeloukas, PMateo, IGwilliam, RCombarros, OArias-Vásquez, AAulchenko, YIkram, MBreteler, Mvan Duijn, COulhaj, AHeun, RIron 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. © 2012 Elsevier Inc. |
| spellingShingle | Lehmann, D Schuur, M Warden, DR Hammond, N Belbin, O Kölsch, H Lehmann, MG Wilcock, G Brown, K Kehoe, P Morris, C Barker, R Coto, E Alvarez, V Deloukas, P Mateo, I Gwilliam, R Combarros, O Arias-Vásquez, A Aulchenko, Y Ikram, M Breteler, M van Duijn, C Oulhaj, A Heun, R Transferrin and HFE genes interact in Alzheimer's disease risk: The Epistasis Project |
| title | Transferrin and HFE genes interact in Alzheimer's disease risk: The Epistasis Project |
| title_full | Transferrin and HFE genes interact in Alzheimer's disease risk: The Epistasis Project |
| title_fullStr | Transferrin and HFE genes interact in Alzheimer's disease risk: The Epistasis Project |
| title_full_unstemmed | Transferrin and HFE genes interact in Alzheimer's disease risk: The Epistasis Project |
| title_short | Transferrin and HFE genes interact in Alzheimer's disease risk: The Epistasis Project |
| title_sort | transferrin and hfe genes interact in alzheimer s disease risk the epistasis project |
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