Department of Neurological Sciences, Dino Ferrari Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
J Alzheimers Dis. 2011;26(4):787-93. doi: 10.3233/JAD-2011-110074.
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.
氧化型低密度脂蛋白受体 1 基因（OLR1）rs1050283 单核苷酸多态性（SNP）先前已被证明与阿尔茨海默病（AD）有关。对 443 名 AD 患者和 393 名年龄匹配的对照组进行了 OLR1 的关联分析。此外，对 20 名患者和 15 名对照组的外周血单核细胞（PBMC）中的 OLR1 及其调节的 hsa-miR369-3p 进行了表达分析。在假设显性模型（CC 和 CT 个体与 TT：p = 0.014，OR：1.50，95%CI：1.08-2.08）和基因型模型（TC 与 TT：p = 0.002，OR：1.61，95%CI：1.14-2.26）下，经过性别和载脂蛋白 E（ApoE）状态调整的逻辑回归分析显示 OLR1 rs1050283 存在统计学显著关联。未观察到患者与对照组之间 OLR1 表达的显著差异（p>0.05）。然而，根据 rs1050283 状态对患者进行分层，与 TT 携带者相比，CC+CT 基因型携带者的 PBMC 中 OLR1 的相对表达水平显著降低（0.13±0.013 与 0.46±0.028，p=0.022），而 hsa-miR369-3p 的相对表达水平无差异（p>0.05）。观察到的影响不是由于载脂蛋白 E ε4 等位基因的存在。OLR1 rs1050283 SNP 可能是散发性 AD 的危险因素。至少存在一个 C 等位基因与 OLR1 mRNA 表达降低相关，而 hsa-miR369-3p 无调节作用，提示多态性等位基因的存在影响 hsa-miR369-3p 与其 3'UTR 保守序列的结合。然而，由于研究的效力有限，需要进一步进行更大样本量的研究。
