The genetic association of miR-34a-5p rs72631823 with the susceptibility to obstetric antiphospholipid syndrome

Obstetric antiphospholipid syndrome (OAPS) is a complex autoimmune disorder affecting women. miR-34a-5p is upregulated in APS patients, yet the role of functional pre-miR-34a rs72631823 polymorphism in OAPS susceptibility and outcomes remains unexplored. This case-control study collected 182 OAPS patients and 188 matched healthy pregnant women (confirmed aPL-negative). The rs72631823 polymorphism was genotyped by TaqMan method. Relative miR-34a-5p level was detected by RT-qPCR. Associations were assessed using Chi-square tests and multivariable logistic regression, presented by odds ratios (ORs) with 95% confidence intervals (CIs). The diagnostic value of miR-34a-5p was evaluated by a receiver operating characteristic (ROC) curve. Bioinformatics analysis of miR-34a-5p target genes was performed using miRDB, TargetScan, and ENCORI databases, followed by GO/KEGG enrichment analysis. rs72631823 AA genotype was independently correlated with increased OAPS risk (adjusted OR = 3.002, 95% CI = 1.189–7.581, P = 0.020), and exhibited a dose-dependent effect on miR-34a-5p expression. The rs72631823 was correlated with a higher risk of poor maternal (AA vs. GG: adjusted OR = 3.767, 95% CI = 1.419–10.003, P = 0.008) and infant outcomes (AA vs. GG: adjusted OR = 2.957, 95% CI = 1.059–8.258, P = 0.039). miR-34a-5p demonstrated promising discriminative ability for OAPS (AUC = 0.859, 95% CI = 0.821–0.897, sensitivity = 79.12%, specificity = 77.66%). Exploratory bioinformatics analysis suggested that miR-34a-5p targets were enriched in Wnt signaling, MAPK pathway, and vascular development. These computational findings provide a plausible biological context and generate hypotheses regarding its potential role in OAPS. miR-34a-5p rs72631823 polymorphism is associated with enhanced miR-34a-5p expression. This increased expression is associated with pro-inflammatory and pro-thrombotic pathways, correlating with an increased risk of OAPS susceptibility and predicting poor outcomes.