Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), "Marqués de Valdecilla" University Hospital (University of Cantabria), Santander, Spain.
Eur J Neurol. 2010 May;17(5):760-2. doi: 10.1111/j.1468-1331.2009.02908.x. Epub 2009 Dec 21.
Oxidative stress is a central factor in the pathogenesis of Parkinson's disease (PD). Heme oxygenase-1 (HO-1) is an antioxidant protein expressed in response to oxidative challenge, and its expression levels are inversely correlated with glycogen synthase kinase-3beta (GSK3beta) activity. Underexpression of HO-1 in concert with an upregulation of GSK3beta would result in a less effective antioxidant response and might increase the risk of PD.
We examined two functional polymorphism in the promoter regions of HO-1 (-413, rs2071746) and GSK3beta (-157, rs6438552) in a group of 251 Spanish patients with PD and 234 controls.
Subjects carrying both the HO-1 (-413, rs2071746) TT genotype and the GSK3beta (-157, rs6438552) TT genotype had a four times higher risk of developing PD than subjects without these genotypes (adjusted by age and sex OR = 4.12; 95% CI = 1.45-11.71; Bonferroni corrected P = 0.024).
Considering synergistic effects between polymorphisms in oxidative stress-related genes may help in determining the risk profile for PD.
氧化应激是帕金森病（PD）发病机制的一个核心因素。血红素加氧酶-1（HO-1）是一种抗氧化蛋白，可响应氧化应激而表达，其表达水平与糖原合酶激酶-3β（GSK3β）活性呈负相关。HO-1 的表达下调与 GSK3β 的上调同时发生，将导致抗氧化反应不那么有效，并且可能增加 PD 的风险。
我们在一组 251 名西班牙 PD 患者和 234 名对照中检查了 HO-1（-413，rs2071746）和 GSK3β（-157，rs6438552）启动子区域的两个功能多态性。
与不携带这些基因型的受试者相比，同时携带 HO-1（-413，rs2071746）TT 基因型和 GSK3β（-157，rs6438552）TT 基因型的受试者患 PD 的风险高四倍（经年龄和性别调整的 OR = 4.12；95%CI = 1.45-11.71；Bonferroni 校正 P = 0.024）。
考虑氧化应激相关基因多态性之间的协同作用可能有助于确定 PD 的风险特征。
