Di Bona Danilo, Candore Giuseppina, Franceschi Claudio, Licastro Federico, Colonna-Romano Giuseppina, Cammà Calogero, Lio Domenico, Caruso Calogero
Dipartimento di Biopatologia e Metodologie Biomediche, University of Palermo, Italy.
Brain Res Rev. 2009 Oct;61(2):60-8. doi: 10.1016/j.brainresrev.2009.05.001. Epub 2009 May 13.
It has been hypothesized that polymorphisms of Tumor Necrosis Factor (TNF)-alpha gene affect the risk of developing Alzheimer's disease (AD). However, results of different studies are often inconsistent. Our aim was to investigate by meta-analysis the association of the common polymorphisms comprehensively defining the genetic variability of the TNF-alpha gene with AD risk. Hence, the results being stated are of a meta-analysis across studies, and that this meta-analysis does not invalidate the results of the individual studies previously performed. Seventeen studies that investigated the association between 5 TNF-alpha polymorphisms (-850, -308, -863, -238, and -1031) and AD were retrieved and analyzed. The model-free approach was applied to meta-analyze these case-control genetic association studies. Available data suggested a significant association between -850 polymorphism and AD risk (TT vs. TC+CC: pooled odds ratio [OR], 1.61; 95% confidence interval [CI], 1.08-2.29; p=0.02) with no evidence of between-study heterogeneity (chi(2), p>0.1). Subgroup analysis suggested that the possession of T allele significantly increased the risk of AD associated with carriage of the apolipoprotein E epsilon 4 allele in Caucasian Australians and Northern Europeans (TT+TC vs. CC: OR, 1.95; 95% CI, 1.45-2.62; p=0.00001; p>0.1; chi(2) for heterogeneity, p>0.1). No significant difference in genotype distribution of -308 polymorphism in AD was found, with a high degree of between-study heterogeneity. For the -863 and -1031 polymorphisms we did not find an association with AD, but significant between-study heterogeneity discouraged genotype data pooling. Only four studies investigated the -238 variant and the results were not significant. Current findings support an association between -850 C>T polymorphism and the risk of developing AD; hence, they strengthen the suggestion of a potential role for anti-TNF therapy to maintain physiologic levels of TNF-alpha.
据推测，肿瘤坏死因子（TNF）-α基因多态性会影响患阿尔茨海默病（AD）的风险。然而，不同研究的结果往往不一致。我们的目的是通过荟萃分析全面研究定义TNF-α基因遗传变异性的常见多态性与AD风险之间的关联。因此，所述结果是跨研究的荟萃分析结果，并且该荟萃分析不会使先前进行的个体研究结果无效。检索并分析了17项研究，这些研究调查了5种TNF-α多态性（-850、-3×8、-863、-238和-1031）与AD之间的关联。采用无模型方法对这些病例对照基因关联研究进行荟萃分析。现有数据表明，-850多态性与AD风险之间存在显著关联（TT与TC+CC相比：合并优势比[OR]，1.61；95%置信区间[CI]，1.08 - 2.29；p = 0.02），且无研究间异质性证据（χ²，p>0.1）。亚组分析表明，在澳大利亚白种人和北欧人中，携带T等位基因显著增加了与载脂蛋白Eε4等位基因携带者相关的AD风险（TT+TC与CC相比：OR，1.95；95%CI，1.45 - 2.62；p = 0.00001；p>0.1；异质性χ²，p>0.1）。未发现AD中-308多态性的基因型分布有显著差异，研究间异质性程度较高。对于-863和-1031多态性，我们未发现与AD有关联，但研究间显著的异质性不鼓励合并基因型数据。仅四项研究调查了-238变体，结果不显著。当前研究结果支持-850 C>T多态性与患AD风险之间的关联；因此，它们强化了抗TNF治疗在维持TNF-α生理水平方面可能发挥作用的观点。
