title: Promoter haplotypes of interleukin-10 gene and sporadic Alzheimer's disease.
abstract: Clinical and immunopathological evidence support a potential role of the pro- and anti-inflammatory cytokine network in neurodegeneration of Alzheimer's disease (AD). Moreover, association studies suggest a possible involvement of cytokine-related genes in the susceptibility to sporadic AD. Since conflicting results are associated with the pro-inflammatory pathway, we investigated a putative effect of the anti-inflammatory counterpart focusing on the interleukin-10 (IL-10) gene. The 5' flanking region contains numerous polymorphisms; in particular, three single nucleotide polymorphisms (-1082 G/A, -819 T/C, -592 C/A) are in linkage disequilibrium resulting in three haplotypes GCC, ACC and ATA. We analyzed the IL-10 haplotype distributions in 215 Italian sporadic AD patients and 153 controls in an association case-control study. Haplotype frequencies did not reveal differences between the two samples, however the genotype GCC/ACC was more represented in AD patients (OR 1.91, 95% CI: 1.18-3.07). This putative risk factor could be independent of the presence of the ApoE epsilon 4 allele. Our results provide new insights on a possible involvement of the IL-10 gene in susceptibility to sporadic AD even though further functional and genetic investigations are necessary to clarify its role in AD.
authors.affiliation: Genetics Unit, I.R.C.C.S. Centro San Giovanni di Dio-Fatebenefratelli, Brescia, Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Scassellati
authors.forename: Roberta
authors.initials: R
authors.lastname: Zanardini
authors.forename: Rosanna
authors.initials: R
authors.lastname: Squitti
authors.forename: Luisella
authors.initials: L
authors.lastname: Bocchio-Chiavetto
authors.forename: Cristian
authors.initials: C
authors.lastname: Bonvicini
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
authors.forename: Orazio
authors.initials: O
authors.lastname: Zanetti
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cassetta
authors.forename: Massimo
authors.initials: M
authors.lastname: Gennarelli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007558:Italy; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D017931:DNA Primers; D016753:Interleukin-10