Genetic Polymorphism of rs13306146 Affects α(2A)AR Expression and Associated With Postpartum Depressive Symptoms in Chinese Women Who Received Cesarean Section

Postpartum depressive symptom (PDS) is a common psychological and mental disorder after giving birth. Our previous studies showing the application of dexmedetomidine, an α(2)-AR agonist, can significantly improve maternal sleep, as well as relieve and reduce the incidence of PDS. This study investigated the association between α(2)(A)AR gene polymorphisms and PDS. A total of 568 cesarean section patients were enrolled; the incidence of PDS is 18.13% (103 with PDS, 465 with non-PDS). The Edinburgh Postpartum Depression Scale score ≥10 was used to diagnose PDS at 42 days after delivery. The single-nucleotide polymorphisms of α(2A)R were sequenced by pyrosequencing. The effect of rs13306146 A > G polymorphism on α(2A)R transcription and the regulation of miR-646 on α(2A)R expression were assessed by dual luciferase reporter assays or gene transfection. Increased stress during pregnancy, poor relationship between mother-in-law and daughter-in-law, spousal relationship, domestic violence, antenatal depression, self-harm ideation, and stressful life events were all associated with increased PDS incidence (p < 0.05). The logistic regression analysis found that the α(2A)AR rs13306146 polymorphism was associated with PDS after adjusting confounding variables. The transcriptional function of the α(2A)AR rs13306146 A allele was decreased compared with the G allele, and the α(2A)AR expression level was correspondingly decreased (p < 0.05), as the strongest binding ability of miR-646 to the α(2A)AR rs13306146 AA genotype. The effect of α(2A)AR rs13306146 A > G polymorphism may change the binding ability of miR-646 at the 3′UTR of the α(2A)AR gene, affecting the expression of α(2A)AR. This study supports the involvement of the norepinephrine system in the pathogenesis of PDS. Genotypes of α(2A)AR may be novel and useful biomarkers for PDS.