Kong Y, Wu J B, Wang X, Zhao J F, Song H, Yuan L D
Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu, China
Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Genet Mol Res. 2014 Dec 4;13(4):10162-72. doi: 10.4238/2014.December.4.10.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that contributes to dementia in the elderly population. Genome-wide linkage analysis has identified chromosome 12p as the AD-susceptible region, which includes lectin-like oxidized low-density lipoprotein receptor 1 (OLR1). The OLR1 +1073 C/T single-nucleotide polymorphism is located in the 3'-untranslated region of the gene and may influence the binding of regulatory microRNAs (miRNAs) and OLR1 protein homeostasis. A number of studies have reported an association between this variant and AD. However, the results are controversial. A meta-analysis of case-control studies examining the relationship between the OLR1 +1073 C/T single-nucleotide polymorphism and AD risk was performed. Five studies were selected that included 2419 cases and 2381 controls. The results revealed a significantly decreased AD risk in the recessive model (TT vs TC + CC: odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.65-0.96). The control group in one of the studies was in Hardy-Weinberg disequilibrium, so we performed additional meta-analysis excluding this study. The significance was much more pronounced in the recessive model (TT vs TC + CC: OR = 0.72, 95%CI = 0.62-0.85). Using miRanda and RNA hybrid methods, the polymorphic allele was shown to influence the binding of various miRNAs. Our results suggested that the +1073 C/T polymorphism decreased the risk of AD. The polymorphic allele was also predicted to affect the binding site of many miRNAs, which may explain the relationship between the +1073 C/T variant and AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，可导致老年人群患痴呆症。全基因组连锁分析已将12号染色体短臂确定为AD易感区域，该区域包含凝集素样氧化型低密度脂蛋白受体1（OLR1）。OLR1 +1073 C/T单核苷酸多态性位于该基因的3'非翻译区，可能影响调控性微小RNA（miRNA）的结合以及OLR1蛋白的稳态。许多研究报道了该变异与AD之间的关联。然而，结果存在争议。我们对病例对照研究进行了荟萃分析，以检验OLR1 +1073 C/T单核苷酸多态性与AD风险之间的关系。我们选择了五项研究，其中包括2419例病例和2381例对照。结果显示，在隐性模型中AD风险显著降低（TT与TC + CC相比：优势比（OR）= 0.79，95%置信区间（CI）= 0.65 - 0.96）。其中一项研究的对照组处于哈迪-温伯格不平衡状态，因此我们排除该研究后进行了额外的荟萃分析。在隐性模型中，显著性更为明显（TT与TC + CC相比：OR = 0.72，95%CI = 0.62 - 0.85）。使用miRanda和RNA杂交方法表明，多态性等位基因会影响各种miRNA的结合。我们的结果表明，+1073 C/T多态性降低了AD风险。多态性等位基因还被预测会影响许多miRNA的结合位点，这可能解释了+1073 C/T变异与AD之间的关系。
