Systematic review by meta-analyses on the possible role of TNF-alpha polymorphisms in association with Alzheimer's disease.

It has been hypothesized that polymorphisms of Tumor Necrosis Factor (TNF)-α gene affectthe risk of developing Alzheimer's disease (AD). However, results of different studies areoften inconsistent. Our aim was to investigate by meta-analysis the association of thecommon polymorphisms comprehensively defining the genetic variability of the TNF-αgene with AD risk. Hence, the results being stated are of a meta-analysis across studies, andthat this meta-analysis does not invalidate the results of the individual studies previouslyperformed. Seventeen studies that investigated the association between 5 TNF-αpolymorphisms (−850, −308, −863, −238, and −1031) and AD were retrieved and analyzed.The model-free approach was applied to meta-analyze these case-control geneticassociation studies. Available data suggested a significant association between −850polymorphism and AD risk (TT vs. TC+CC: pooled odds ratio [OR], 1.61; 95% confidenceinterval [CI], 1.08–2.29; p=0.02) with no evidence of between-study heterogeneity (χ2, p>0.1).Subgroup analysis suggested that the possession of T allele significantly increased the riskof AD associated with carriage of the apolipoprotein E ɛ4 allele in Caucasian Australians andNorthern Europeans (TT+TC vs. CC: OR, 1.95; 95% CI, 1.45–2.62; p=0.00001; p>0.1; χ2 forheterogeneity, p>0.1). No significant difference in genotype distribution of −308polymorphism in AD was found, with a high degree of between-study heterogeneity. Forthe −863 and −1031 polymorphisms we did not find an association with AD, but significantbetween-study heterogeneity discouraged genotype data pooling. Only four studiesinvestigated the −238 variant and the results were not significant. Current findingssupport 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 maintainphysiologic levels of TNF-α.