Role of OLR1 and its regulating hsa-miR369-3p in Alzheimer's disease: genetics and expression analysis

Document Type

Article

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.

Medical Subject Headings

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)

Publication Date

1-1-2011

Publication Title

Journal of Alzheimer's disease : JAD

E-ISSN

1875-8908

Volume

26

Issue

4

First Page

787

Last Page

93

PubMed ID

21709374

Digital Object Identifier (DOI)

10.3233/JAD-2011-110074

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