Interleukin-10 promoter polymorphism in sporadic Alzheimer's disease.
Proinflammatory cytokines and acute-phase proteins play an important role in Alzheimer's disease (AD) neurodegeneration, and common polymorphisms of genes controlling their high production have been shown to be associated with AD. Thus, AD patients display a proinflammatory genotype and the control of inflammation might play a protective role in AD development. By sequence-specific probes, we have evaluated the role of anti-inflammatory cytokine interleukin(IL)-10 in AD, by analysing in 132 AD patients and 213 healthy controls the prevalence of three different haplotypes, involving three single-nucleotide polymorphisms (SNPs) at -1082 (G-->A), -819 (C-->T) and -592 (C-->A) nucleotides of IL-10 promoter, associated with different IL-10 production. The percentage of -1082A carrier subjects was significantly increased among AD patients, and this increase was mainly due to the increase of ATA haplotype. Analysing these results according to the well-known genetic risk factor APOE-e4 allele, no significant differences were observed in SNP IL-10 allele distribution between AD patients carrying the genotype or not. So we may conclude that the presence of -1082A allele and in particular of -1082A/-819T/-592A haplotype, associated with a low production of anti-inflammatory cytokine IL-10, may be considered as an additive and independent genetic risk factor for AD.
Lio
D
D
Gruppo di Studio sull'Immunosenescenza, Dipartimento di Biopatologia e Metodologie Biomediche, Università di Palermo, Italy.
Licastro
F
F
Scola
L
L
Chiappelli
M
M
Grimaldi
L M
LM
Crivello
A
A
Colonna-Romano
G
G
Candore
G
G
Franceschi
C
C
Caruso
C
C
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic
D016753:Interleukin-10