title: Polymorphism of the OLR1 3'UTR potential microRNA binding site and risk of Alzheimer's disease: a meta-analysis.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu, China kongyancn@gmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: J B
authors.initials: JB
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: J F
authors.initials: JF
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: H
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: L D
authors.initials: LD
authors.lastname: Yuan
mesh_terms: D020413:3' Untranslated Regions; D000544:Alzheimer Disease / Q000235:genetics*; D001665:Binding Sites; D016022:Case-Control Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C495137:OLR1 protein, human; D012333:RNA, Messenger; D051127:Scavenger Receptors, Class E