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: Maria Serpente, Chiara Fenoglio, Chiara Villa, Francesca Cortini, Claudia Cantoni, Elisa Ridolfi, Francesca Clerici, Alessandra Marcone, Luisa Benussi, Roberta Ghidoni, Filippo Martinelli Boneschi, Salvatore Gallone, Stefano Cappa, Giuliano Binetti, Massimo Franceschi, Innocenzo Rainero, Maria Teresa Giordana, Claudio Mariani, Nereo Bresolin, Elio Scarpini, Daniela Galimberti
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 26 Issue 4 Pg. 787-93 ( 2011) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 21709374 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• MIRN369 microRNA, human
• MicroRNAs
• OLR1 protein, human
• RNA, Messenger
• Scavenger Receptors, Class E
• DNA

Topics

• Age of Onset
• Aged
• Alleles
• Alzheimer Disease (genetics)
• Apolipoproteins E (genetics)
• DNA (genetics, isolation & purification)
• Female
• Gene Expression Regulation (genetics)
• Genotype
• Humans
• Italy
• Male
• MicroRNAs (genetics)
• Monocytes (drug effects)
• Neuropsychological Tests
• Polymorphism, Single Nucleotide (genetics)
• RNA, Messenger (biosynthesis, genetics)
• Real-Time Polymerase Chain Reaction
• Scavenger Receptors, Class E (genetics)