Associations between Certain Polymorphisms in Proinflammatory Cytokines and Predisposition of Alzheimer's Disease: A Meta-Analysis

Background: Functional gene polymorphisms of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-18 (IL-18) may contribute to the onset and development of Alzheimer's disease (AD), but the relationships between these polymorphisms and predisposition of AD remain controversial. Objectives: This meta-analysis was conducted to more robustly assess relationships between TNF-alpha/IL-6/IL-8/IL-18 polymorphisms and predisposition of AD by pooling the findings of relevant studies. Methods: A comprehensive literature searching was performed in PubMed, Embase, Web of Science, Wanfang, and CNKI databases, and 63 studies were found to be eligible for quantitative analyses. Results: The pooled meta-analysis results showed that genotypic frequencies of TNF-alpha rs1800629, IL-6 rs1800795, IL-8 rs4073, and IL-18 rs187238 polymorphisms among AD cases and controls of Asian ethnicity differed significantly. But, we did not observe such genotypic frequencies differences in Caucasians. Conclusions: This meta-analysis suggests that TNF-alpha rs1800629, IL-6 rs1800795, IL-8 rs4073, and IL-18 rs187238 polymorphisms may affect predisposition of AD in Asians, but not in Caucasians.