A functional SNP rs895819 on pre-miR-27a is associated with bipolar disorder by targeting NCAM1

Abstract

The aberrant expression or genomic mutations of microRNA are associated with several human diseases. This study analyzes the relationship between genetic variations of miRNA and schizophrenia or bipolar disorder. We performed case-control studies for ten SNPs in a total sample of 1584 subjects. All these ten SNPs were on or near mature microRNAs. We identified the association between bipolar disorder and the T/C polymorphism at rs895819. To illustrate the function of miR-27a, we constructed several miR-27a knockout (KO) cell lines, determined candidates of miR-27a, and then verified NCAM1 as a target gene of miR-27a. Further studies revealed that the T/C polymorphism on miR-27a led to the differential expression of mature and precursor miR-27a without affecting the expression of primary miR-27a. Furthermore, the C mutation on pre-miR-27a suppresses cell migration and dopamine expression levels. Our study highlights the importance of miR-27a and its polymorphism at rs895819 in bipolar disorder.

A Functional Single Nucleotide Polymorphism in the 3′ Untranslated Region of the Porcine JARID2 Gene Is Associated with Aggressive Behavior of Weaned Pigs after Mixing

“…For example, the rs1321204 site on the serotonin receptor 1B (HTR1B) gene regulates the expression of HTR1B by affecting the binding of miR-96 to HTR1B, thus affecting the aggressive behavior of mice [ 28 ]. SNP rs895819, located on pre-miR-27a, is involved in the regulation of bipolar disorder by targeting neural cell adhesion molecule 1 (NCAM1) [ 29 ].…”

Genetic Variation in miR-27a Is Associated with Fluoropyrimidine-Associated Toxicity in Patients with Dihydropyrimidine Dehydrogenase Variants after Genotype-Guided Dose Reduction

“…However, the mechanism of the rs895819 SNV and its effect on its expression is unknown. Previous studies suggested that the rs895819 SNV alters the stability and/or processing of miR-27a; however, these results are conflicting, with some studies showing increased miR-27a expression [13,34], others showing decreased miR-27a expression [27,35,36], and one showing no effect of the rs895819 SNV on miR-27a expression [37]. Similarly, conflicting studies have shown a decrease, an increase, and no association between carriers of the rs895819 SNV and the risk of various cancers [16][17][18]25,38].…”