两个氧化应激相关基因（血红素加氧酶-1 和 GSK3β）对帕金森病风险的协同作用。
Synergistic effect of two oxidative stress-related genes (heme oxygenase-1 and GSK3β) on the risk of Parkinson's disease.
机构信息
Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), "Marqués de Valdecilla" University Hospital (University of Cantabria), Santander, Spain.
出版信息
Eur J Neurol. 2010 May;17(5):760-2. doi: 10.1111/j.1468-1331.2009.02908.x. Epub 2009 Dec 21.
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSIONS
Considering synergistic effects between polymorphisms in oxidative stress-related genes may help in determining the risk profile for PD.
背景
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。
方法
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。
结果
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）。
结论
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。
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