title: Interleukin-10 and interleukin-6 gene polymorphisms as risk factors for Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Geriatrics, Ospedale Maggiore IRCCS, University of Milano, Milan, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Arosio
authors.forename: Daria
authors.initials: D
authors.lastname: Trabattoni
authors.forename: Lorenza
authors.initials: L
authors.lastname: Galimberti
authors.forename: Paolo
authors.initials: P
authors.lastname: Bucciarelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Fasano
authors.forename: Carmen
authors.initials: C
authors.lastname: Calabresi
authors.forename: Carlo Lorenzo
authors.initials: CL
authors.lastname: Cazzullo
authors.forename: Carlo
authors.initials: C
authors.lastname: Vergani
authors.forename: Giorgio
authors.initials: G
authors.lastname: Annoni
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: 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
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015850:Interleukin-6; D016753:Interleukin-10