Association between miR-182 rs76481776 Polymorphism and Antidepressant Treatment Response in Patients with Depression

The efficacy of antidepressants is influenced by a combination of genetic, individual, and environmental factors. This study aimed to investigate the association between the miR-182 rs76481776 polymorphism and the response to antidepressant treatment in major depressive disorder (MDD) patients, and its underlying molecular mechanisms.

This study enrolled 180 MDD patients and 180 healthy controls. The rs76481776 genotype was determined using TaqMan-based qPCR. The severity of depression and treatment response were assessed using the Hamilton Depression Rating Scale (HAMD). The expression of miR-182 and BDNF was measured using RT-qPCR. The regulatory relationship between miR-182 and BDNF was confirmed through a luciferase reporter gene assay. The correlation between miR-182 and BDNF expression was evaluated using the Pearson correlation coefficient.

The T allele of rs76481776 was a significant risk factor for MDD (OR = 2.182, 95% CI: 1.424-3.345, p < 0.001) and was significantly associated with higher baseline scores on the HAMD. Moreover, individuals carrying the T allele (CT/TT genotype) exhibited a significantly poorer response to antidepressant treatment and a lower remission rate within 12 months compared to those with the CC genotype (p < 0.05). Mechanistically, miR-182 was highly expressed in patients with MDD (p < 0.05), and its expression was even higher in T allele carriers (p < 0.05). miR-182 could directly target and suppress BDNF , leading to decreased BDNF expression in MDD patients, and its expression was significantly and inversely correlated with BDNF expression.

The T allele of rs76481776 diminished the therapeutic efficacy of antidepressants by up-regulating miR-182 expression and subsequently suppressing BDNF expression.