title: Genetics and expression analysis of the specificity protein 4 gene (SP4) in patients with Alzheimer's disease and frontotemporal lobar degeneration.
abstract: Transcription factor Sp4 (Specificity protein 4) levels are increased in the brain of patients with Alzheimer's disease (AD), and Sp4 colocalizes with neurofibrillary tangles. Moreover, SP4 is a susceptibility gene for bipolar disorder and schizophrenia, which share many clinical features with frontotemporal lobar degeneration (FTLD). The distribution of three tagging single nucleotide polymorphisms(SNPs)-rs9639379, rs10272006, and rs6461569-has been determined in a population of 352 patients diagnosed clinically with AD, 290 patients with FTLD, and 341 age-matched controls. Expression analysis of SP4 was performed in peripheral blood mononuclear cells (PBMC). No significant differences in either allelic or genotypic frequency of the three SNPs were found (p > 0.05), even stratifying according to gender and to the apolipoprotein E status. Significantly increased SP4 relative expression levels were observed in PBMC from patients with AD as compared with controls (7.132 ± 1.301 versus 3.396 ± 0.829, p < 0.050) and a similar trend was shown in patients with FTLD compared with controls (6.525 ± 1.500 versus 3.396 ± 0.829, p = 0.073). According to these results, SP4 gene does not act as a susceptibility factor either for AD or FTLD. However, Sp4 mRNA levels are upregulated in patients, possibly resulting in an aberrant expression of downstream target genes involved in the pathogenesis of both diseases.
authors.affiliation: Department of Neurological Sciences, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.forename: Laura
authors.initials: L
authors.lastname: Ghezzi
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Francesca
authors.initials: F
authors.lastname: Clerici
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marcone
authors.forename: Luisa
authors.initials: L
authors.lastname: Benussi
authors.forename: Roberta
authors.initials: R
authors.lastname: Ghidoni
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gallone
authors.forename: Maria
authors.initials: M
authors.lastname: Serpente
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.forename: Elisa
authors.initials: E
authors.lastname: Ridolfi
authors.forename: Rossana
authors.initials: R
authors.lastname: Bonsi
authors.forename: Chiara
authors.initials: C
authors.lastname: Cerami
authors.forename: Stefano
authors.initials: S
authors.lastname: Cappa
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Franceschi
authors.forename: Innocenzo
authors.initials: I
authors.lastname: Rainero
authors.forename: Claudio
authors.initials: C
authors.lastname: Mariani
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
mesh_terms: D000368:Aged; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D008297:Male; D051706:Sp4 Transcription Factor / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: C497124:SP4 protein, human; D051706:Sp4 Transcription Factor