Association of QPRT gene polymorphisms with postpartum depression in Chinese cesarean parturients: A candidate gene...

Postpartum depression (PPD) is a common and serious mental disorder after childbirth, imposing a heavy burden on mothers, infants, and families. Abnormalities in the tryptophan-kynurenine (TRP-KYN) metabolic pathway are considered to be involved in its pathogenesis, but the role of quinolinic acid phosphoribosyltransferase (QPRT), a key downstream enzyme in this pathway, remains unclear. This study aims to explore the association between PPD in women undergoing cesarean section and QPRT gene polymorphisms, as well as other risk factors for PPD.

A candidate gene association study design was adopted. From January 2024 to June 2025, full-term singleton pregnant women scheduled to undergo elective cesarean section under spinal anesthesia were recruited at the Third Xiangya Hospital of Central South University and Hunan Provincial Maternal and Child Health Hospital. At 42 days postpartum, postpartum depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS). Peripheral blood samples were collected and genomic DNA was extracted. Four QPRT single nucleotide polymorphism loci (rs1134700, rs2303255, rs9922666, and rs9933310) were selected for genotyping to analyze the association between these loci and PPD. Bioinformatics analysis and dual-luciferase reporter gene assays were performed to investigate the possible mechanism by which significant loci influence disease occurrence.

A total of 362 women were ultimately included in the analysis, among whom 29 were diagnosed with PPD, with an incidence of 8.01%. Analysis of general data showed that comorbid hypertension or thyroid disease, inconsistency between neonatal sex and expectation, prenatal depression, prenatal self-harm ideation, domestic violence, poor marital and mother-in-law/daughter-in-law relationships, stressful life events, dissatisfaction with current life status, poor mood during pregnancy, and high stress during pregnancy were all risk factors for PPD in women undergoing cesarean section (all P<0.05). Genetic association analysis revealed that the QPRT rs9933310 A>G polymorphism was associated with PPD. Women carrying the rs9933310 GG or AG genotype had a 2.92-fold higher risk of PPD compared with women with the AA genotype (OR=2.92, 95% CI 1.18 to 6.99). Expression quantitative trait loci (eQTL) analysis suggested that the G allele at this locus was associated with downregulation of QPRT expression (AA>AG>GG). Multi-database queries indicated that the rs9933310 locus may have promoter and/or enhancer activity. In addition, JASPAR database prediction and experimental validation showed that the mutant (G) allele at the QPRT rs9933310 locus was more likely than the wild-type (A) allele to weaken promoter-enhancer activity at this locus, and resulted in loss of transcription factors Gata1, GATA2, GATA3, Gata4, Sox17, Sox2, Sox3, Sox6, and SRY, thereby regulating QPRT expression.

Comorbid hypertension or thyroid disease, inconsistency between neonatal sex and expectation, prenatal depression, prenatal self-harm ideation, domestic violence, poor marital and mother-in-law/daughter-in-law relationships, stressful life events, dissatisfaction with current life status, poor mood during pregnancy, high stress during pregnancy, and mutation at the QPRT rs9933310 locus are all risk factors for PPD. The QPRT rs9933310 G allele is an independent risk factor for PPD in women undergoing cesarean section, and its pathogenic mechanism may involve downregulation of QPRT expression and disruption of TRP-KYN pathway homeostasis. QPRT has a potential role in the pathogenesis of PPD and may become a novel antidepressant target acting on the TRP-KYN pathway.