Research Article

Polymorphism of the OLR1 3'UTR potential microRNA binding site and risk of Alzheimer’s disease: a meta-analysis

Published: December 04, 2014
Genet. Mol. Res. 13 (4) : 10162-10172 DOI: https://doi.org/10.4238/2014.December.4.10
Cite this Article:
Y. Kong, J.B. Wu, X. Wang, J.F. Zhao, H. Song, L.D. Yuan (2014). Polymorphism of the OLR1 3'UTR potential microRNA binding site and risk of Alzheimer’s disease: a meta-analysis. Genet. Mol. Res. 13(4): 10162-10172. https://doi.org/10.4238/2014.December.4.10
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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.

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.