Genetics and expression analysis of the specificity protein 4 gene (SP4) in patients with Alzheimer's disease and frontotemporal lobar degeneration
Document Type
Article
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.
Medical Subject Headings
Aged; Female; Frontotemporal Lobar Degeneration (genetics, metabolism, pathology); Gene Expression Regulation; Genotype; Humans; Male; Sp4 Transcription Factor (biosynthesis, metabolism)
Publication Date
1-1-2012
Publication Title
Journal of Alzheimer's disease : JAD
E-ISSN
1875-8908
Volume
31
Issue
3
First Page
537
Last Page
42
PubMed ID
22614877
Digital Object Identifier (DOI)
10.3233/JAD-2012-120379
Recommended Citation
Villa, Chiara; Ghezzi, Laura; Fenoglio, Chiara; Clerici, Francesca; Marcone, Alessandra; Benussi, Luisa; Ghidoni, Roberta; Gallone, Salvatore; Serpente, Maria; Cantoni, Claudia; Ridolfi, Elisa; Bonsi, Rossana; Cerami, Chiara; Cappa, Stefano; Binetti, Giuliano; Franceschi, Massimo; Rainero, Innocenzo; Mariani, Claudio; Bresolin, Nereo; Scarpini, Elio; and Galimberti, Daniela, "Genetics and expression analysis of the specificity protein 4 gene (SP4) in patients with Alzheimer's disease and frontotemporal lobar degeneration" (2012). Translational Neuroscience. 2333.
https://scholar.barrowneuro.org/neurobiology/2333