MicroRNA in Alzheimer’s Disease: Results of interaction analysis

Abstract

AbstractBackgroundMiRNA are multifunctional molecules involved in regulating posttranscriptional expression of genes. Several studies showed that miR‐107 influences expression of the BACE1 gene in the process of Aβ production. Extracellular accumulation of Aβ is well‐known hallmark of Alzheimer’s disease (AD). The product NLRP3 gene is involved in inflammasome that induces neuroinflammation a pathological process accompanying AD. The role of miR‐107 in regulation of NRLP3 is unknown.MethodWe used logistic regression model with the interaction term to test the hypothesis that interaction of SNPs from miR‐107 with SNPs from the NLRP3 gene is associated with AD. For this we used data on genotyped individuals collected in Framingham Health Study (FHS). The Cardiovascular Health Study (CHS) was used to replicate the research findings. Linkage Disequilibrium test and clumping procedure were used to reduce the number of tests and make Bonferroni correction less conservative.ResultIn the analysis of FHS data we found that the association of the rs2926616 SNP from the miR‐107 miRNA with the rs10754557 SNP from the NLRP3 gene is positive and statistically significant. The effect size β = 0.356, p‐value 6.71E‐03. This value is smaller than the p‐value threshold calculated in accordance with Bonferroni correction 7.14E‐03. This result is replicated in the analysis of CHS data with β = 0.289, and p‐value 4.76E‐02. Using FHS data we also tested the role of interaction of SNPs from the miR‐107 with SNPs from the TLR2 gene in AD and found a pair of SNPs whose interaction has statistically significant association with AD. This finding was replicated in the analysis of the CHS data where an interaction of a pair of SNPs also showed significant association with AD. Detected SNPs from this pair were in linkage disequilibrium with the pair SNPs from the CHS data.ConclusionThe results of these analyses indicate that one miRNA may influence several components of AD pathological development. This property may have important implications for developing efficient medications against AD. More studies are needed to evaluate miRNA involvement in different pathways of AD regulation, as well as in identifying factors capable in affecting such miRNA.