title: Effect of proinflammatory gene polymorphisms on the risk of Alzheimer's disease.
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.
  
  
  CONCLUSIONS
  Proinflammatory genotypes might influence the development and progression of AD exerting a potential synergistic effect.
authors.affiliation: Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Flex
authors.forename: Silvia
authors.initials: S
authors.lastname: Giovannini
authors.forename: Federico
authors.initials: F
authors.lastname: Biscetti
authors.forename: Rosa
authors.initials: R
authors.lastname: Liperoti
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Spalletta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Straface
authors.forename: Francesco
authors.initials: F
authors.lastname: Landi
authors.forename: Flavia
authors.initials: F
authors.lastname: Angelini
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ghirlanda
authors.forename: Roberto
authors.initials: R
authors.lastname: Bernabei
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D015703:Antigens, CD / Q000235:genetics; D002097:C-Reactive Protein / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D002097:C-Reactive Protein; D020781:Matrix Metalloproteinase 1