A Functional SNP rs895819 on Pre-miR-27a is Associated with Bipolar Disorder by Targeting ICAM-1.

Abstract

Aberrant expression or genomic mutations of microRNA have been reported to be associated with a variety of human diseases. This study is aimed to analyze the association between genetic variations of miRNA and schizophrenia or bipolar disorder. We performed case-control studies for ten SNPs in a total sample of 1584 Chinese subjects. All these ten SNPs are on or near mature microRNAs which are expressed in the brain. To illustrate the function of miR-27a, we constructed a miR-27a knockout (KO) astrocytoma cell line U-251MG. By comparing the differentially expressed genes in wild-type and KO U-251MG, we determined several candidate target genes of miR-27a and then verified ICAM-1 as a target gene of miR-27a. We identified the association between the T/C polymorphism at rs895819 and bipolar disorder. Ectopic expression of miR-27a in NPCs showed that the T to C mutation at rs895819 reduced the suppressive effects of miR-27a on the expression of its target genes. Further studies revealed that the T/C polymorphism on miR-27a led to differential expression of mature and precursor miR-27a without affecting the expression of primary miR-27a. Our study highlighted the importance of miR-27a and its polymorphism at rs895819 in bipolar disorder.