Role of hnRNP-A1 and miR-590-3p in neuronal death: genetics and expression analysis in patients with Alzheimer disease and frontotemporal lobar degeneration
Document Type
Article
Abstract
An association study of heterogeneous nuclear ribonucleoprotein (hnRNP)-A1 was carried out in a population of 274 patients with frontotemporal lobar degeneration (FTLD) and 287 with Alzheimer disease (AD) as compared with 344 age- and gender-matched controls. In addition, we evaluated expression levels of hnRNP-A1 and its regulatory microRNA (miR)-590-3p in blood cells from patients and controls. A statistically significant increased frequency of the hnRNP-A1 rs7967622 C/C genotype was observed in FTLD, but not in AD, in patients as compared to controls (23.0 versus 15.4%; p = 0.022, odds ratio [OR] 1.64, confidence interval [CI] 1.09-2.46). Stratifying according to gender, a statistically significant increased frequency of the hnRNP-A1 rs7967622 C/C genotype was observed in male patients as compared to male controls (23.1 versus 11.3%; p = 0.015, OR 2.36, CI 1.22-4.58 but not in females. Considering the rs4016671 single-nucleotide polymorphism (SNP), all patients and controls were wild type. Significantly increased hnRNP-A1 relative expression levels in peripheral blood mononuclear cells (PBMCs) was observed in patients with AD, but not with FTLD, as compared to controls (2.724 ± 0.570 versus 1.076 ± 0.187, p = 0.021). Decreased relative expression levels of hsa-miR-590-3p was observed in patients with AD versus controls (0.685 ± 0.080 versus 0.931 ± 0.111, p = 0.079), and correlated negatively with hnRNP-A1 mRNA levels (r = -0.615, p = 0.0237). According to these findings, hnRNP-A1 and its transcription regulatory factor miR-590-3p are disregulated in patients with AD, and the hnRNP-A1 rs7967622 C/C genotype is likely a risk factor for FTLD in male populations.
Medical Subject Headings
Aged; Alleles; Alzheimer Disease (genetics, pathology); Base Sequence; Case-Control Studies; Cell Death; Female; Frontotemporal Lobar Degeneration (genetics, pathology); Gene Expression Regulation; Gene Frequency (genetics); Heterogeneous Nuclear Ribonucleoprotein A1; Heterogeneous-Nuclear Ribonucleoprotein Group A-B (blood, genetics); Humans; Male; MicroRNAs (blood, genetics); Molecular Sequence Data; Neurons (metabolism, pathology); Polymorphism, Single Nucleotide (genetics); Sequence Alignment
Publication Date
6-1-2011
Publication Title
Rejuvenation research
E-ISSN
1557-8577
Volume
14
Issue
3
First Page
275
Last Page
81
PubMed ID
21548758
Digital Object Identifier (DOI)
10.1089/rej.2010.1123
Recommended Citation
Villa, Chiara; Fenoglio, Chiara; De Riz, Milena; Clerici, Francesca; Marcone, Alessandra; Benussi, Luisa; Ghidoni, Roberta; Gallone, Salvatore; Cortini, Francesca; Serpente, Maria; Cantoni, Claudia; Fumagalli, Giorgio; Martinelli Boneschi, Filippo; Cappa, Stefano; Binetti, Giuliano; Franceschi, Massimo; Rainero, Innocenzo; Giordana, Maria Teresa; Mariani, Claudio; Bresolin, Nereo; Scarpini, Elio; and Galimberti, Daniela, "Role of hnRNP-A1 and miR-590-3p in neuronal death: genetics and expression analysis in patients with Alzheimer disease and frontotemporal lobar degeneration" (2011). Translational Neuroscience. 2344.
https://scholar.barrowneuro.org/neurobiology/2344