TY - JOUR
T1 - Role of OLR1 and its regulating hsa-miR369-3p in Alzheimer's disease
T2 - Genetics and expression analysis
AU - Serpente, Maria
AU - Fenoglio, Chiara
AU - Villa, Chiara
AU - Cortini, Francesca
AU - Cantoni, Claudia
AU - Ridolfi, Elisa
AU - Clerici, Francesca
AU - Marcone, Alessandra
AU - Benussi, Luisa
AU - Ghidoni, Roberta
AU - Boneschi, Filippo Martinelli
AU - Gallone, Salvatore
AU - Cappa, Stefano
AU - Binetti, Giuliano
AU - Franceschi, Massimo
AU - Rainero, Innocenzo
AU - Giordana, Maria Teresa
AU - Mariani, Claudio
AU - Bresolin, Nereo
AU - Scarpini, Elio
AU - Galimberti, Daniela
PY - 2011
Y1 - 2011
N2 - 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 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.
AB - 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 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.
KW - Alzheimer's disease
KW - hsa-miR369-3p
KW - OLR1
KW - oxidized LDL receptor 1
KW - peripheral mononuclear blood cells
KW - single nucleotide polymorphism
UR - http://www.scopus.com/inward/record.url?scp=80055033952&partnerID=8YFLogxK
U2 - 10.3233/JAD-2011-110074
DO - 10.3233/JAD-2011-110074
M3 - Article
C2 - 21709374
AN - SCOPUS:80055033952
SN - 1387-2877
VL - 26
SP - 787
EP - 793
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -