Effect of proinflammatory gene polymorphisms on the risk of Alzheimer's disease

Andrea Flex, Silvia Giovannini, Federico Biscetti, Rosa Liperoti, Gianfranco Spalletta, Giuseppe Straface, Francesco Landi, Flavia Angelini, Carlo Caltagirone, Giovanni Ghirlanda, Roberto Bernabei

Research output: Contribution to journalArticle

Abstract

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 polymorphisms of genes encoding prototypical inflammatory molecules in individuals with AD. We also investigated whether a synergistic effect of these proinflammatory gene polymorphisms 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 1β (IL1B) -31 T/C, tumor necrosis factor α (TNF-α) -308 G/A, macrophage migration inhibitory factor (MIF) -173 G/C, monocyte chemoattractant protein 1 (CCL2) -2518 A/G, intercellular adhesion molecule 1 (ICAM1) 469 E/K, E-selectin (SELE) Ser128Arg, macrophage inflammatory protein 1α (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 polymorphisms 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: Proinflammatory genotypes might influence the development and progression of AD exerting a potential synergistic effect.

Original languageEnglish
Pages (from-to)230-236
Number of pages7
JournalNeurodegenerative Diseases
Volume13
Issue number4
DOIs
Publication statusPublished - 2014

Keywords

  • Alzheimer's disease
  • Gene polymorphism
  • Inflammation

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)

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  • Cite this

    Flex, A., Giovannini, S., Biscetti, F., Liperoti, R., Spalletta, G., Straface, G., Landi, F., Angelini, F., Caltagirone, C., Ghirlanda, G., & Bernabei, R. (2014). Effect of proinflammatory gene polymorphisms on the risk of Alzheimer's disease. Neurodegenerative Diseases, 13(4), 230-236. https://doi.org/10.1159/000353395