Role of hnRNP-A1 and miR-590-3p in neuronal death: Genetics and expression analysis in patients with alzheimer disease and frontotemporal lobar degeneration

Chiara Villa, Chiara Fenoglio, Milena De Riz, Francesca Clerici, Alessandra Marcone, Luisa Benussi, Roberta Ghidoni, Salvatore Gallone, Francesca Cortini, Maria Serpente, Claudia Cantoni, Giorgio Fumagalli, Filippo Martinelli Boneschi, Stefano Cappa, Giuliano Binetti, Massimo Franceschi, Innocenzo Rainero, Maria Teresa Giordana, Claudio Mariani, Nereo BresolinElio Scarpini, Daniela Galimberti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)275-281
Number of pages7
JournalRejuvenation Research
Volume14
Issue number3
DOIs
Publication statusPublished - Jun 1 2011

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

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