title: Role of hnRNP-A1 and miR-590-3p in neuronal death: genetics and expression analysis in patients with Alzheimer disease and frontotemporal lobar degeneration.
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.
authors.affiliation: Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Milena
authors.initials: M
authors.lastname: De Riz
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: Francesca
authors.initials: F
authors.lastname: Cortini
authors.forename: Maria
authors.initials: M
authors.lastname: Serpente
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fumagalli
authors.forename: Filippo
authors.initials: F
authors.lastname: Martinelli Boneschi
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: Maria Teresa
authors.initials: MT
authors.lastname: Giordana
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; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D016022:Case-Control Studies; D016923:Cell Death; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation; D005787:Gene Frequency / Q000235:genetics; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; C568221:MIRN590 microRNA, human; D035683:MicroRNAs