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

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.