Mateo Ignacio, Sánchez-Juan Pascual, Rodríguez-Rodríguez Eloy, Infante Jon, Vázquez-Higuera José Luis, García-Gorostiaga Inés, Berciano José, Combarros Onofre
Neurology Service, University Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain.
Dement Geriatr Cogn Disord. 2008;26(4):339-42. doi: 10.1159/000161059. Epub 2008 Oct 8.
Oxidative stress plays a role in tau hyperphosphorylation and the development of neurofibrillary tangles (NFT). In Alzheimer's disease (AD) brain, accumulation of hyperphosphorylated tau in NFT is associated with the induction of heme oxygenase-1 (HO-1), a potent antioxidant that downregulates the production of tau. In a case-control study of 300 AD patients and 360 healthy controls, we examined whether the combined gene effects between HO-1 (-413, rs2071746) and tau (5' of exon 1, rs242557) polymorphisms might be responsible for susceptibility to AD. Subjects carrying both the HO-1 (-413) TT and the tau (5' of exon 1) AA genotypes had a more than 6.5-time higher risk of developing AD than subjects without these risk genotypes (OR = 6.65, 95% CI 1.12-39.29; p = 0.037). These data support a role for tau-related genes in the risk of AD.
氧化应激在tau蛋白过度磷酸化和神经原纤维缠结（NFT）的形成过程中发挥作用。在阿尔茨海默病（AD）患者的大脑中，NFT内过度磷酸化tau蛋白的积累与血红素加氧酶-1（HO-1）的诱导有关，HO-1是一种有效的抗氧化剂，可下调tau蛋白的产生。在一项针对300例AD患者和360例健康对照的病例对照研究中，我们检测了HO-1（-413，rs2071746）和tau（外显子1的5'端，rs242557）基因多态性的联合效应是否可能与AD易感性有关。同时携带HO-1（-413）TT和tau（外显子1的5'端）AA基因型的受试者患AD的风险比没有这些风险基因型的受试者高6.5倍以上（比值比=6.65，95%置信区间1.12-39.29；p=0.037）。这些数据支持tau相关基因在AD风险中发挥作用。
