Wang Binbin, Zhou Sirui, Yang Ze, Xie Yan-Chen, Wang Jing, Zhang Peng, Lv Zeping, Zheng Chenguang, Ma Xu
National Research Institute for Family Planning, Beijing, 100081 China.
J Neurol Sci. 2008 Jul 15;270(1-2):148-51. doi: 10.1016/j.jns.2008.02.021. Epub 2008 Apr 8.
Neuroinflammation and abnormal phosphorylation of TAU proteins have been implicated in the etiology of Alzheimer's disease (AD). Several studies have suggested the G-308A promoter polymorphism in one of the proinflammatory cytokine genes tumor necrosis factor-alpha (TNF-alpha) encoding TNF-alpha may be associated with AD pathogenesis. Association between the Q7R polymorphism in saitohin (STH), a gene nested within the intron of the Tau gene, has also been reported. To determine whether these two polymorphisms contribute to the risk for late-onset AD (LOAD) in Chinese, we have investigated 207 sporadic LOAD patients and 222 healthy controls. The associations of the AA genotype and A-allele with LOAD (chi(2) = 8.74, df = 1, P = 0.0031, and chi(2) = 4.47, df = 1, P = 0.035) were found. After stratifying by apolipoprotein E allele 4 (APOE epsilon4) status, increased LOAD risks associated with the AA genotype and A-allele only in the APOE epsilon4 non-carriers (chi(2) = 9.21, df = 1, P = 0.002; chi(2) = 10.02, df = 1, P = 0.0015) were seen. These results suggested that the TNF-alpha gene G-308A polymorphism might be a risk factor for LOAD and dependent on APOE epsilon4 status in Chinese. Homozygous Q/Q of STH Q7R polymorphism was the only one genotype found in either LOAD group or controls. No R allele was detected in LOAD and control groups. The extremely rare frequency of the ancestral R allele differs sharply from that observed in studies in the Caucasian population, suggesting obvious ethnic differences.
神经炎症和TAU蛋白的异常磷酸化与阿尔茨海默病（AD）的病因有关。多项研究表明，促炎细胞因子基因之一肿瘤坏死因子-α（TNF-α）编码TNF-α的G-308A启动子多态性可能与AD发病机制相关。也有报道称，位于Tau基因内含子中的saitohin（STH）基因的Q7R多态性之间存在关联。为了确定这两种多态性是否会增加中国晚发性AD（LOAD）的风险，我们调查了207例散发性LOAD患者和222例健康对照。发现AA基因型和A等位基因与LOAD相关（χ² = 8.74，自由度 = 1，P = 0.0031，χ² = 4.47，自由度 = 1，P = 0.035）。按载脂蛋白E等位基因4（APOE ε4）状态分层后，仅在APOE ε4非携带者中观察到AA基因型和A等位基因与LOAD风险增加相关（χ² = 9.21，自由度 = 1，P = 0.002；χ² = 10.02，自由度 = 1，P = 0.0015）。这些结果表明，TNF-α基因G-308A多态性可能是LOAD的一个风险因素，且在中国人群中依赖于APOE ε4状态。STH Q7R多态性的纯合子Q/Q是LOAD组或对照组中唯一发现的基因型。在LOAD组和对照组中均未检测到R等位基因。祖先R等位基因的频率极低，与在白种人群体中的研究结果明显不同，表明存在明显的种族差异。
