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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Published Online First 13 February 2007
Competing interests: None.