转铁蛋白和 HFE 基因在阿尔茨海默病风险中相互作用：连锁研究项目。

Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project.

机构信息

Oxford Project to Investigate Memory and Ageing, University Department of Physiology, Anatomy and Genetics, Oxford, UK.

出版信息

Neurobiol Aging. 2012 Jan;33(1):202.e1-13. doi: 10.1016/j.neurobiolaging.2010.07.018. Epub 2010 Sep 2.

DOI:10.1016/j.neurobiolaging.2010.07.018

PMID:20817350

Abstract

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.

摘要

铁过载可能导致阿尔茨海默病（AD）的风险增加。在 Epistasis 项目中，我们研究了 2 个铁代谢基因中的 4 个变体：血色病（HFE）C282Y 和 H63D，以及转铁蛋白（TF）C2 和 -2G/A，该项目纳入了 1757 例 AD 病例和 6295 例对照。我们复制了先前报道的 HFE 282Y 与 TF C2 在 AD 风险中的相互作用：协同因子为 1.75（95%置信区间，1.1-2.8，p = 0.02），在北欧人群中。在携带 APOEε4 等位基因的人群中，协同因子为 3.1（1.4-6.9；0.007）。我们发现了另一个相互作用，即 HFE 63HH 与 TF -2AA，该相互作用明显受年龄影响。这两种相互作用主要或仅在北欧人群中发现。HFE 282Y 与 TF C2 的相互作用已在总共 2313 例 AD 病例和 7065 例对照中被复制了两次，并且与铁负荷增加有关。因此，我们认为铁过载可能是 AD 发展的一个致病因素。在某些情况下，铁过载的治疗可能具有保护作用。