TY - JOUR
T1 - Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease
AU - Combarros, Onofre
AU - van Duijn, Cornelia M
AU - Hammond, Naomi
AU - Belbin, Olivia
AU - Arias-Vásquez, Alejandro
AU - Cortina-Borja, Mario
AU - Lehmann, Michael G
AU - Aulchenko, Yurii S
AU - Schuur, Maaike
AU - Kölsch, Heike
AU - Heun, Reinhard
AU - Wilcock, Gordon K
AU - Brown, Kristelle
AU - Kehoe, Patrick G
AU - Harrison, Rachel
AU - Coto, Eliecer
AU - Alvarez, Victoria
AU - Deloukas, Panos
AU - Mateo, Ignacio
AU - Gwilliam, Rhian
AU - Morgan, Kevin
AU - Warden, Donald R
AU - Smith, A David
AU - Lehmann, Donald J
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
U2 - 10.1186/1742-2094-6-22
DO - 10.1186/1742-2094-6-22
M3 - Article (Academic Journal)
C2 - 19698145
SN - 1742-2094
VL - 6
SP - 22
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
ER -