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

Journal article

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 x 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 epsilon4 (APOEepsilon4) 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.

Authors: Combarros, O; van Duijn, C; Hammond, N; Belbin, O; Arias-Vásquez, A

• Publication status: Published
• Journal: Journal of neuroinflammation
• Volume: 6
• Issue: 1
• Pages: 22
• Publication date: 2009-01-01
• DOI: 10.1186/1742-2094-6-22
• EISSN: 1742-2094
• ISSN: 1742-2094
• Language: English
• Keywords: Encephalitis; Humans; Genetic Testing; Gene Expression Regulation; Polymorphism, Genetic; Aged; Risk Factors; Epistasis, Genetic; Brain; Interleukin-10; Genetic Predisposition to Disease; Genotype; Interleukin-6; Aged, 80 and over; Brain Chemistry; DNA Mutational Analysis; Alzheimer Disease; Female; Male