Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer's disease.
In the pathogenesis of Alzheimer disease (AD), it has been proposed that the anti-inflammatory interleukins such as IL-10 regulate beta-amyloid-induced microglial inflammatory responses inhibiting the proinflammatory cytokine IL-6. Since the promoters of the IL-10 and IL-6 genes show single nucleotide polymorphisms (SNPs) (IL-10: -1082 G --> A; IL-6: -174 G --> C), we investigated these SNPs and cytokine production by peripheral blood mononuclear cells in 65 AD patients and 65 controls (HC). In AD there was a significant increase of the -1082A IL-10 allele (P=0.009) and a decrease of -1082GG genotype (P=0.019). The frequency of the GG IL-6 genotype in AD was lower and the C allele significantly higher (P <0.005). The co-occurrence of IL-10 A and IL-6 C alleles significantly raised the odds ratio (OR 11.2, confidence interval: CI 1.3-97.3; P <0.05) independently of apolipoprotein E4 (adjusted OR 10.3, CI 1-108; P <0.05). Only amyloid-stimulated IL-10 production differed between the groups (P=0.023). These results raise questions regarding the inflammatory theory in AD, pointing to a pivotal role of IL-10 and IL-6 and a selective alteration in this network.
Arosio
Beatrice
B
Department of Geriatrics, Ospedale Maggiore IRCCS, University of Milano, Milan, Italy.
Trabattoni
Daria
D
Galimberti
Lorenza
L
Bucciarelli
Paolo
P
Fasano
Francesca
F
Calabresi
Carmen
C
Cazzullo
Carlo Lorenzo
CL
Vergani
Carlo
C
Annoni
Giorgio
G
Clerici
Mario
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004660:Encephalitis / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology; D007558:Italy; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015850:Interleukin-6; D016753:Interleukin-10