Interleukin 18 gene polymorphisms predict risk and outcome of Alzheimer's disease

Paola Bossù, Antonio Ciaramella, Maria Luisa Moro, Lorenza Bellincampi, Sergio Bernardini, Giorgio Federici, Alberto Trequattrini, Fabio Macciardi, Ilaria Spoletini, Fulvia Di Iulio, Carlo Caltagirone, Gianfranco Spalletta

Research output: Contribution to journalArticle

Abstract

Background and aim: Inflammation has been extensively implicated in the pathogenesis of Alzheimer's disease (AD). Although there is evidence of a key role for cytokines in neuroinflammation processes, so far the proinflammatory cytokine interleukin (IL)-18 has not been associated with AD. The aim of this study was to investigate the impact of two polymorphisms of the human IL-18 gene promoter at positions -607 (C/A) and -137 (G/C) on both susceptibility to and progression of AD. Results: The results revealed that the genotype distribution of the -607 (C/A) polymorphism was different between patients with AD and control subjects (χ2 = 7.99, df = 2, p = 0.0184). In particular, carriers of the CC genotype were at increased risk of developing AD (OR 2.33; 95% CI 1.29 to 4.22; p = 0.0052). The observed genotypes were in Hardy-Weinberg equilibrium, as for the -607 polymorphism, whereas the -137 polymorphism appeared in Hardy-Weinberg disequilibrium only in the patient group (p = 0.0061). Finally, in a 2 year follow-up study, the -137 CC 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 apolipoprotein E ε4/non-ε4 allele presence. Conclusion: As 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.

Original languageEnglish
Pages (from-to)807-811
Number of pages5
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume78
Issue number8
DOIs
Publication statusPublished - Aug 2007

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)
  • Psychiatry and Mental health

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    Bossù, P., Ciaramella, A., Moro, M. L., Bellincampi, L., Bernardini, S., Federici, G., Trequattrini, A., Macciardi, F., Spoletini, I., Di Iulio, F., Caltagirone, C., & Spalletta, G. (2007). Interleukin 18 gene polymorphisms predict risk and outcome of Alzheimer's disease. Journal of Neurology, Neurosurgery and Psychiatry, 78(8), 807-811. https://doi.org/10.1136/jnnp.2006.103242