title: Candidate gene analysis of IP-10 gene in patients with Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Neurological Sciences, Dino Ferrari Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Venturelli
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Carlo
authors.initials: C
authors.lastname: Lovati
authors.forename: Dario
authors.initials: D
authors.lastname: Finazzi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guidi
authors.forename: Barbara
authors.initials: B
authors.lastname: Corrà
authors.forename: Diego
authors.initials: D
authors.lastname: Scalabrini
authors.forename: Francesca
authors.initials: F
authors.lastname: Clerici
authors.forename: Claudio
authors.initials: C
authors.lastname: Mariani
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
mesh_terms: 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
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D017931:DNA Primers