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Interleukin-18 gene polymorphisms predict risk and outcome of Alzheimer's disease
  1. Paola Bossù (p.bossu{at}hsantalucia.it)
  1. IRCCS Santa Lucia Foundation, Italy
    1. Antonio Ciaramella
    1. IRCCS Santa Lucia Foundation, Italy
      1. Maria Luisa Moro
      1. IRCCS Santa Lucia Foundation, Italy
        1. Lorenza Bellincampi
        1. University of Rome Tor Vergata, Italy
          1. Sergio Bernardini
          1. University of Rome Tor Vergata, Italy
            1. Giorgio Federici
            1. University of Rome Tor Vergata, Italy
              1. Alberto Trequattrini
              1. ASL Città di Castello, PG, Italy
                1. Fabio Macciardi
                1. University of Milano, Italy
                  1. Ilaria Spoletini
                  1. IRCCS Santa Lucia Foundation, Italy
                    1. Fulvia Di Iulio
                    1. IRCCS Santa Lucia Foundation, Italy
                      1. Carlo Caltagirone (c.caltagirone{at}hsantalucia.it)
                      1. IRCCS Santa Lucia Foundation, Italy
                        1. Gianfranco Spalletta (g.spalletta{at}hsantalucia.it)
                        1. IRCCS Fondazione Santa Lucia, Italy

                          Abstract

                          Inflammation has been extensively implicated in Alzheimer's disease (AD) pathogenesis. Although there is evidence of a key role for cytokines in neuroinflammation processes, so far the pro-inflammatory cytokine IL-18 has not yet been associated to AD. This study was aimed to investigate the impact of two polymorphisms of human IL-18 gene promoter at positions - 607 (C/A) and -137 (G/C) on both susceptibility to and progression of AD. The results revealed that the genotype distribution of -607 (C/A) polymorphism was different between AD patients and control subjects (chi- square=7.99, df= 2, p=0.0184). In particular, carriers of CC genotype were at increased risk of developing AD (OR=2.33; 95% CI=1.28-4.21; p=0.0052). The observed genotypes were in Hardy-Weinberg equilibrium as for -607 polymorphism, whereas the -137 polymorphism appeared in Hardy-Weinberg disequilibrium only in patient group (p=0.0061). Finally, in a two year follow up study, the - 137 C/C genotype was strongly and specifically associated with a faster cognitive decline (F=4.024; df=4,192; p=0.0037 for time by IL-18 -137 G/C group interaction) with no interaction effect with the ApoE epsilon 4/non epsilon 4 allele presence. Since IL-18 cytokine promoter gene polymorphisms have been previously described to have functional consequences on IL-18 expression, it is possible that individuals with a prevalent IL-18 gene variant have a dysregulated immune response, suggesting that IL-18 mediated immune mechanisms may play a crucial role in AD.

                          • alzheimer’s disease
                          • cytokine polymorphisms
                          • inflammation
                          • interleukin-18

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