Interleukin-6 (IL-6), identified as a pleiotropic inflammatory cytokine, plays important roles in the acute inflammatory response and in the modulation of the neuroimmune response. To date, large amounts of epidemiological studies have been performed to investigate the association between the IL-6 -174G/C polymorphism and Alzheimer's disease (AD) risk. Inconclusive results, however, have been reported. We aimed to assess the effect of the IL-6 -174G/C polymorphism on AD susceptibility with the use of a meta-analysis. 14 studies involving 3769 cases of AD and 9431 control subjects were identified by a search of Pubmed, Embase and ISI Web of Science databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) for the IL-6 -174G/C polymorphism and AD risk were computed using fixed- or random-effects model when appropriate. Obvious heterogeneity among studies was detected, and a borderline statistically significant association was observed between the IL-6 -174G/C polymorphism and AD risk in Caucasians (GG vs. CC: OR=1.35, 95%CI, 1.06-1.72; GG/GC vs. CC: OR=1.27, 95%CI, 1.05-1.53, respectively). After exclusion of one study, the heterogeneity disappeared and no significant association was observed between the polymorphism and AD risk. These findings indicate that the IL-6 -174G/C polymorphism may not be an independent risk factor for the development of AD.
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