Candidate gene analysis of IP-10 gene in patients with Alzheimer's disease.
Interferon-gamma-inducible Protein-10 (IP-10) is supposed to play a role in Alzheimer's disease (AD) development, as demonstrated by increased levels in cerebrospinal fluid from patients with AD. A mutation scanning of IP-10 exonic region was carried out in 10 patients with AD and 10 age-matched controls, demonstrating the presence of two previously reported single nucleotide polymorphisms (SNPs) in exon 4 (G-->C and T-->C) as well as a novel SNP in exon 2 (C-->T). Exon 4 G-->C and T-->C allelic variants were next evaluated in a population of 279 AD patients and 251 controls, in order to determine whether their presence could influence the susceptibility towards the development of the disease. These two SNPs were in complete linkage disequilibrium. No differences in haplotype frequencies were found in AD patients as compared with controls, even stratifying according to the presence of Apolipoprotein E varepsilon4 allele, gender or age at onset. A new protocol was developed to easily determine the C-->T SNP in exon 2. A preliminary analysis revealed a very low frequency of this allelic variant (1%). Therefore, the complete association study was not carried out because the size of our population was not sufficient to draw reliable conclusions. According to these results, IP-10 does not seem to be a risk factor for AD. However, a novel rare polymorphism has been identified, which could exert a role in AD susceptibility. Thus, further studies on larger populations are needed before confidently excluding IP-10 as a susceptibility gene for AD.
Venturelli
Eliana
E
Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Italy.
Galimberti
Daniela
D
Fenoglio
Chiara
C
Lovati
Carlo
C
Finazzi
Dario
D
Guidi
Ilaria
I
Corrà
Barbara
B
Scalabrini
Diego
D
Clerici
Francesca
F
Mariani
Claudio
C
Forloni
Gianluigi
G
Bresolin
Nereo
N
Scarpini
Elio
E
D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D001483:Base Sequence; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics*; D017931:DNA Primers; D005091:Exons; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D017931:DNA Primers