Role of OLR1 and Its Regulating hsa-miR369-3p in Alzheimer's Disease: Genetics and Expression Analysis

Article type: Research Article

Authors: Serpente, Maria^a | Fenoglio, Chiara^a | Villa, Chiara^a | Cortini, Francesca^a | Cantoni, Claudia^a | Ridolfi, Elisa^a | Clerici, Francesca^b | Marcone, Alessandra^c | Benussi, Luisa^d | Ghidoni, Roberta^{d; e} | Boneschi, Filippo Martinelli^{f; g} | Gallone, Salvatore^h | Cappa, Stefano^{c; f; i} | Binetti, Giuliano^d | Franceschi, Massimo^j | Rainero, Innocenzo^h | Giordana, Maria Teresa^h | Mariani, Claudio^b | Bresolin, Nereo^a | Scarpini, Elio^a | Galimberti, Daniela^{a; *}

Affiliations: [a] Department of Neurological Sciences, “Dino Ferrari” Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy | [b] Center for Research and Treatment on Cognitive Dysfunctions, Chair of Neurology, University of Milan, “Luigi Sacco” Hospital, Milan, Italy | [c] Division of Neurology, San Raffaele Turro Hospital, Milan, Italy | [d] NeuroBioGen-Lab-Memory Clinic, IRCCS Centro S.Giovanni di Dio-FBF, Brescia, Italy | [e] Proteomics Unit, IRCCS Centro S. Giovanni di Dio-FBF, Brescia, Italy | [f] Department of Neurology, Scientific Institute San Raffaele, Milan, Italy | [g] Institute of Experimental Neurology (INSPE), Milan, Italy | [h] Department of Neuroscience, University of Turin, Turin, Italy | [i] Vita-Salute San Raffaele University, Milan, Italy | [j] Clinica Neurologica, Casa di Cura Santa Maria di Castellanza (Varese), Italy

Correspondence: [*] Correspondence to: Daniela Galimberti, Dept. of Neurological Sciences, “Dino Ferrari” Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy. Tel.: +39.2.55033847; Fax: +39.2.50320430; E-mail: daniela.galimberti@unimi.it.

Abstract: The oxidized LDL receptor 1 gene (OLR1) rs1050283 single nucleotide polymorphism (SNP) has been previously shown to be associated with Alzheimer's disease (AD). An association analysis of OLR1 was carried out in a population of 443 patients with AD as compared with 393 age-matched controls. In addition, an expression analysis of OLR1 and its regulatory hsa-miR369-3p was performed in peripheral mononuclear blood cells (PBMC) from 20 patients and 15 controls. Logistic regression analysis, adjusted for gender and apolipoprotein E (ApoE) status, showed a statistically significant association of OLR1 rs1050283 under the assumption of a dominant model (CC and CT individuals versus TT: p = 0.014, OR: 1.50, 95%CI: 1.08–2.08) and a genotypic model (TC versus TT: p = 0.002, OR: 1.61, 95%CI: 1.14–2.26). No significant differences in OLR1 expression was observed between patients and controls (p > 0.05). However, stratifying patients according to the rs1050283 status, significantly decreased relative PBMC expression levels of OLR1 were observed in carriers of CC+CT genotypes as compared with TT carriers (0.13 ± 0.013 versus 0.46 ± 0.028, p = 0.022), whereas no differences in relative expression levels of the hsa-miR369-3p were observed (p > 0.05). The effect observed was not due to the presence of the ApoE ε4 allele. The OLR1 rs1050283 SNP likely acts as a risk factor for sporadic AD. The presence of at least one C allele is associated with a decreased expression of OLR1 mRNA in the absence of hsa-miR369-3p de-regulation, suggesting that the presence of the polymorphic allele influences the binding of hsa-miR369-3p to its 3'UTR consensus sequence. Nevertheless, the limited power of the study requires further investigations with a larger sample size.

Keywords: Alzheimer's disease, hsa-miR369-3p, oxidized LDL receptor 1, OLR1, peripheral mononuclear blood cells, single nucleotide polymorphism

DOI: 10.3233/JAD-2011-110074

Journal: Journal of Alzheimer's Disease, vol. 26, no. 4, pp. 787-793, 2011