Introduction: Depression is a prevalent mental health disorder. miR-27a regulates neuronal development. This study aimed to investigate the association between the miR-27a rs895819 polymorphism and antidepressant treatment response in patients with depression. Methods: The expression level of miR-27a was detected by reverse transcription-polymerase chain reaction. The genotype of rs895819 was performed by PCR-restriction fragment length polymorphism. The condition of patients was evaluated by a 17-item Hamilton Depression Rating Scale (HAMD-17) (reduction rate = [HAMD-17 baseline − HAMD-17 8 weeks]/HAMD-17 baseline × 100%). Effective response was defined as a reduction rate of ≥50%. Remission was defined as HAMD-17 ≤17. The association between SNP and depression risk was calculated by the χ2 test. Logistic regression analysis was performed to evaluate the effects of SNP on antidepressant treatment response. Results: There were 173 patients with depression and 186 healthy controls. rs895819 was negatively correlated with depression under CC versus TT (p = 0.044, OR = 0.412, 95% CI = 0.170–0.996), CC + TC versus TT (OR = 0.607, 95% CI = 0.397–0.927), and C versus T (OR = 0.633, 95% CI = 0.448–0.896) models. miR-27a expression was significantly decreased in individuals with TC/CC genotypes than TT genotypes. rs895819 (TC/CC) was positively correlated with the effective response (p = 0.005, OR = 2.551, 95% CI = 1.322–4.920). Conclusion: rs895819 TC/CC genotypes were significantly correlated with depression and associated with increased effective response.

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