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


CONCLUSIONS
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.
Combarros
Onofre
O
Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Marqués de Valdecilla University Hospital (University of Cantabria), 39008 Santander, Spain. combarro@unican.es
van Duijn
Cornelia M
CM
Hammond
Naomi
N
Belbin
Olivia
O
Arias-Vásquez
Alejandro
A
Cortina-Borja
Mario
M
Lehmann
Michael G
MG
Aulchenko
Yurii S
YS
Schuur
Maaike
M
Kölsch
Heike
H
Heun
Reinhard
R
Wilcock
Gordon K
GK
Brown
Kristelle
K
Kehoe
Patrick G
PG
Harrison
Rachel
R
Coto
Eliecer
E
Alvarez
Victoria
V
Deloukas
Panos
P
Mateo
Ignacio
I
Gwilliam
Rhian
R
Morgan
Kevin
K
Warden
Donald R
DR
Smith
A David
AD
Lehmann
Donald J
DJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics / Q000276:immunology; D004252:DNA Mutational Analysis; D004660:Encephalitis / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors
D015850:Interleukin-6; D016753:Interleukin-10
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