Genetic Polymorphism of rs13306146 Affects α2AAR Expression and Associated With Postpartum Depressive Symptoms in Chinese Women Who Received Cesarean Section

Abstract

Postpartum depressive symptom (PDS) is a common psychological and mental disorder after giving birth. Our previous studies showing the application of dexmedetomidine, an α2-AR agonist, can significantly improve maternal sleep, as well as relieve and reduce the incidence of PDS. This study investigated the association between α2AAR 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 α2AR were sequenced by pyrosequencing. The effect of rs13306146 A > G polymorphism on α2AR transcription and the regulation of miR-646 on α2AR 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 α2AAR rs13306146 polymorphism was associated with PDS after adjusting confounding variables. The transcriptional function of the α2AAR rs13306146 A allele was decreased compared with the G allele, and the α2AAR expression level was correspondingly decreased (p < 0.05), as the strongest binding ability of miR-646 to the α2AAR rs13306146 AA genotype. The effect of α2AAR rs13306146 A > G polymorphism may change the binding ability of miR-646 at the 3′UTR of the α2AAR gene, affecting the expression of α2AAR. This study supports the involvement of the norepinephrine system in the pathogenesis of PDS. Genotypes of α2AAR may be novel and useful biomarkers for PDS.

Genetic Markers Associated with Postpartum Depression: A Review

“…That study reported that women with the α2AAR rs13316046AA genotype have a significantly greater risk of PPD than women with the AG and GG genotypes. 26 The observed effect of the A > G polymorphism may be attributed to changes in the binding capacity of miR-646, which affects the transcription levels of α2AAR . 26 PPD symptoms are significantly associated with specific SIRT2 and SIRT6 polymorphisms.…”

“… 26 The observed effect of the A > G polymorphism may be attributed to changes in the binding capacity of miR-646, which affects the transcription levels of α2AAR . 26 PPD symptoms are significantly associated with specific SIRT2 and SIRT6 polymorphisms. The SIRT2 polymorphisms at rs2873703 (TT genotype) and rs4801933 (TT genotype), as well as the SIRT6 polymorphisms at rs350846 (CC genotype) and rs107251 (TT genotype), are correlated with PPD symptoms (p < 0.05).…”

Exploring the Relationship Between Circadian Rhythm Shifts and Postpartum Depression

“…Genetic factors are also thought to play a role in the susceptibility to PPD. Certain genetic variations, including variations in clock genes that regulate circadian rhythms, have been associated with an increased risk of PPD [32,33]. These genetic factors may influence an individual's sensitivity to circadian rhythm disturbances and their subsequent impact on mood and mental health.…”

Effect of Dexmedetomidine on Postpartum Depression in Women With Prenatal Depression

“…The role of the α 2 -AR is also indicated by preclinical data, with dexmedetomidine significantly improving depression-like behavior in sleep-deprived mice . Previous data show an α 2 -AR gene alteration to be associated with PPD susceptibility . Many studies have also confirmed that dexmedetomidine can upregulate brain-derived neurotrophic factor (BDNF), which is closely related to the pathogenesis and prognosis of PPD .…”

“…11 Previous data show an α 2 -AR gene alteration to be associated with PPD susceptibility. 12 Many studies have also confirmed that dexmedetomidine can upregulate brain-derived neurotrophic factor (BDNF), 13,14 which is closely related to the pathogenesis and prognosis of PPD. 15,16 Autry et al 17 also reported that the rapid antidepressive-like effects of ketamine were dependent on the rapid synthesis of BDNF.…”