Association of MIR137 rs1625579 polymorphisms with cognitive function in patients with untreated first-episode depression.

Abstract

Background: Depression arises from genetic and environmental factors, and it may lead to cognitive dysfunction. This study aimed to explore the relationship between microRNA-137 (miR-137) and the MIR137 rs1625579 polymorphism and cognitive function in depression.

Methods: This study enrolled 190 healthy controls and 340 untreated first-episode depressed patients, with the latter stratified into non-cognitive impairment (n = 134) and cognitive impairment (n = 206) subgroups. Genotyping of the MIR137 rs1625579 locus was performed using TaqMan polymerase chain reaction (PCR), while miR-137 expression was quantified via reverse transcription quantitative PCR (RT-qPCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the core biological functions and key signaling pathways associated with miR-137 target genes. RNA pull-down assay, RNA immunoprecipitation (RIP) assay, and a dual luciferase assay were used to verify the targeted binding relationship between miR-137 and GSK3B.

Results: miR-137 expression was significantly downregulated in depressed patients with cognitive impairment. The G allele (TG/GG genotype) of the MIR137 rs1625579 was identified as a protective factor for cognitive impairment in depression patients, whereas the T allele (TT genotype) was an independent risk factor. Reduced miR-137 expression was closely related to depression and cognitive impairment, exhibiting promising discriminatory capacity in this study, and warrants further validation as a candidate biomarker for both. Moreover, miR-137 expression was negatively correlated with the degree of depression (Hamilton Depression Rating Scale (HAMD) score) in depression patients and positively correlated with cognitive function (Montreal Cognitive Assessment (MoCA) / Mini-Mental State Examination (MMSE) score). Mechanistically, in vitro experiments confirmed that miR-137 directly targeted GSK3B, and elevated GSK3B expression observed in patients was significantly correlated with cognitive impairment in depression. In depressed patients with cognitive impairment, individuals carrying the G allele showed relatively higher miR-137 expression and lower GSK3B expression compared to TT carriers, suggesting a potential protective association. However, owing to the cross-sectional design, these clinical findings should be interpreted as correlational associations rather than definite in vivo mechanistic proof.

Conclusion: The MIR137 rs1625579 polymorphism was associated with cognitive function in depression, and this association may be related to the miR-137/GSK3B axis.