Effect of Proinflammatory Gene Polymorphisms on the Risk of Alzheimer's Disease

Background: A number of studies associate Alzheimer's disease (AD) with APOE polymorphism and alleles which favor the increased expression of immunological mediators such as cytokines or acute-phase proteins. Objective: In this study we evaluated the distribution of a set of functionally important polynnorphisms of genes encoding prototypical inflammatory molecules in individuals with AD. We also investigated whether a synergistic effect of these proinflammatory gene polynnorphisms on the risk of AD could be hypothesized. Methods: In a genetic association study that included 533 AD patients and 713 controls, the following gene polymorphisms were analyzed: C-reactive protein (CRP) 1059 G/C, interleukin 6 (IL6) -174 G/C, interleukin 1 beta (IL1B) -31 TIC, tumor necrosis factor a (TNF-alpha) -308 G/A, macrophage migration inhibitory factor (MIF) -173 G/C, monocyte chennoattractant protein 1 (CCL2) -2518 A/G, intercellular adhesion molecule 1 (ICAM1) 469 E/K, E-selectin (SELE) Ser128Arg, macrophage inflammatory protein la (CCL3) -906 T/A, matrix metalloproteinase 3 (MMP3) -1171 5A/6A and matrix metalloproteinase 9 (MMP9) -1562 C/T. Results: We found that IL6, IL1B, CCL2, CCL3, SELE, ICAM1, MMP3, and MMP9 gene polynnorphisms were significantly and independently associated with AD. The association remained significant even after the Bonferroni correction. We also found that these proinflammatory polymorphisms were associated with different levels of risk for AD, depending on the number of high-risk genotypes concomitantly carried by a given individual. Conclusion: Proinflannmatory genotypes might influence the development and progression of AD exerting a potential synergistic effect. Copyright (C) 2013 S. Karger AG, Basel