title: Role of OLR1 and its regulating hsa-miR369-3p in Alzheimer's disease: genetics and expression analysis.
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.
authors.affiliation: Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Serpente
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.forename: Francesca
authors.initials: F
authors.lastname: Cortini
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.forename: Elisa
authors.initials: E
authors.lastname: Ridolfi
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: Filippo
authors.initials: F
authors.lastname: Martinelli Boneschi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gallone
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: D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009000:Monocytes / Q000187:drug effects; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; C560308:MIRN369 microRNA, human; D035683:MicroRNAs; C495137:OLR1 protein, human; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E; D004247:DNA