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.
|Titolo:||Role of OLR1 and its regulating hsa-miR369-3p in Alzheimer’s disease : genetics and expression analysis|
|Parole Chiave:||Age of Onset; Aged; Alleles; Alzheimer Disease; Apolipoproteins E; DNA; Female; Gene Expression Regulation; Genotype; Humans; Italy; Male; MicroRNAs; Monocytes; Neuropsychological Tests; Polymorphism, Single Nucleotide; RNA, Messenger; Real-Time Polymerase Chain Reaction; Scavenger Receptors, Class E; hsa-miR369-3p; oxidized LDL receptor 1; OLR1; peripheral mononuclear blood cells; single nucleotide polymorphism|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Data di pubblicazione:||2011|
|Digital Object Identifier (DOI):||10.3233/JAD-2011-110074|
|Appare nelle tipologie:||01 - Articolo su periodico|