TY - JOUR
T1 - Genetics and expression analysis of the specificity protein 4 gene (SP4) in patients with Alzheimer's disease and frontotemporal lobar degeneration
AU - Villa, Chiara
AU - Ghezzi, Laura
AU - Fenoglio, Chiara
AU - Clerici, Francesca
AU - Marcone, Alessandra
AU - Benussi, Luisa
AU - Ghidoni, Roberta
AU - Gallone, Salvatore
AU - Serpente, Maria
AU - Cantoni, Claudia
AU - Ridolfi, Elisa
AU - Bonsi, Rossana
AU - Cerami, Chiara
AU - Cappa, Stefano
AU - Binetti, Giuliano
AU - Franceschi, Massimo
AU - Rainero, Innocenzo
AU - Mariani, Claudio
AU - Bresolin, Nereo
AU - Scarpini, Elio
AU - Galimberti, Daniela
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - expression
KW - frontotemporal lobar degeneration
KW - risk factor
KW - SP4
KW - specificity protein 4
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U2 - 10.3233/JAD-2012-120379
DO - 10.3233/JAD-2012-120379
M3 - Article
C2 - 22614877
AN - SCOPUS:84865591172
VL - 31
SP - 537
EP - 542
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
SN - 1387-2877
IS - 3
ER -