Allele frequencies of +874T --> A single nucleotide polymorphism at the first intron of IFN-gamma gene in Alzheimer's disease patients.
OBJECTIVE
Inflammation seems to play a role in progressive neurological degenerative diseases such as Alzheimer's disease (AD). Local inflammatory processes can in fact give rise to direct neurotoxicity, interfere with beta-amyloid expression and metabolism, and maintain chronic, intracerebral, acute-phase protein secretion, in turn favoring the formation of beta-amyloid fibrils. Accordingly, recent studies show an increased risk for AD associated with certain polymorphisms in the genes encoding some proinflammatory cytokines and acute-phase proteins. To our knowledge, no data have yet been presented on the association between AD and polymorphisms of the interferon(IFN)-gamma gene, despite the pivotal role that IFN-gamma plays in immune-mediated inflammatory responses.


METHODS
Using the amplification refractory mutation system method, we evaluated the role of IFN-gamma in AD by analyzing, in 111 AD patients and 213 healthy controls, the prevalence of +874T --> A single nucleotide polymorphism (SNP), associated with different IFN-gamma production. Allele ApoE polymorphisms were assessed by the PCR-based method.


RESULTS
No statistically significant differences were observed between AD patients and controls in the frequency of +874T --> A SNP, either on analyzing data as a whole or according to gender. As expected, the frequency of the well-known genetic risk factor APOE-epsilon4 allele was significantly increased in AD patients. However, analyzing the results according to the presence or absence of the APOE-epsilon4 allele, no interactions among ApoE, IFN-gamma alleles, gender or age at onset were observed.


CONCLUSIONS
Our study does not support the hypothesis that IFN-gamma SNP may be a genetic risk factor for AD. Further analysis of recently described IFN-gamma polymorphisms may clarify the role, if any, of IFN-gamma alleles in AD.
Scola
Letizia
L
Gruppo di Studio sull'Immunosenescenza, Department of Pathobiology and Biomedical Methodologies, University of Palermo, Palermo, Italy.
Licastro
Federico
F
Chiappelli
Martina
M
Franceschi
Claudio
C
Grimaldi
Luigi M
LM
Crivello
Antonio
A
Colonna-Romano
Giuseppina
G
Candore
Giuseppina
G
Lio
Domenico
D
Caruso
Calogero
C
D000225:Adenine; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012016:Reference Values; D012727:Sex Characteristics; D013941:Thymine
D017931:DNA Primers; D007371:Interferon-gamma; D000225:Adenine; D013941:Thymine