Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease

Onofre Combarros, Cornelia M van Duijn, Naomi Hammond, Olivia Belbin, Alejandro Arias-Vásquez, Mario Cortina-Borja, Michael G Lehmann, Yurii S Aulchenko, Maaike Schuur, Heike Kölsch, Reinhard Heun, Gordon K Wilcock, Kristelle Brown, Patrick G Kehoe, Rachel Harrison, Eliecer Coto, Victoria Alvarez, Panos Deloukas, Ignacio Mateo, Rhian GwilliamKevin Morgan, Donald R Warden, A David Smith, Donald J Lehmann

Research output: Contribution to journalArticle (Academic Journal)peer-review

45 Citations (Scopus)

Abstract

Background Chronic inflammation is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10). Methods We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls. Results We replicated the interaction. For IL6 rs2069837 AA × IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10–2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E ε4 (APOEε4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded. Conclusion We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD.
Translated title of the contributionReplication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease
Original languageEnglish
Pages (from-to)22
JournalJournal of Neuroinflammation
Volume6
DOIs
Publication statusPublished - Aug 2009

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