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Interleukin 18 gene polymorphisms predict risk and outcome of Alzheimer’s disease
  1. Paola Bossù1,
  2. Antonio Ciaramella1,
  3. Maria Luisa Moro1,
  4. Lorenza Bellincampi2,
  5. Sergio Bernardini2,
  6. Giorgio Federici2,
  7. Alberto Trequattrini3,
  8. Fabio Macciardi4,
  9. Ilaria Spoletini1,
  10. Fulvia Di Iulio1,
  11. Carlo Caltagirone1,
  12. Gianfranco Spalletta1
  1. 1IRCCS Santa Lucia Foundation, Rome, Italy
  2. 2Department of Internal Medicine and Department of Laboratory Medicine, University “Tor Vergata”, Rome, Italy
  3. 3ASL Città di Castello, Perugia, Italy
  4. 4Policlinico MultiMedica and Department of Science and Biomedical Technologies, University of Milano, Italy
  1. Correspondence to:
 Dr Paola Bossù
 IRCCS Santa Lucia Foundation, Department of Clinical and Behavioural Neurology, Experimental Neuro-psychobiology Lab, Via Ardeatina, 306, I-00179 Roma, Italy; p.bossu{at}hsantalucia.it

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.

  • Aβ, amyloid beta peptide
  • AD, Alzheimer’s disease
  • ApoE, apolipoprotein E
  • IL, interleukin
  • MMSE, Mini Mental State Examination
  • NINCDS-ADRDA, National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer’s Disease and Related Disorders Association

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Footnotes

  • Published Online First 13 February 2007

  • Competing interests: None.

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