ArticleMolecular biology reports2026
Epigenetic regulation of HLA-G : implications for recurrent pregnancy loss.
Article in Molecular biology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundRecurrent pregnancy loss (RPL) is a multifactorial reproductive disorder in which epigenetic dysregulation has been increasingly implicated. DNA methylation of immune-regulatory genes, particularly human leukocyte antigen-G (HLA-G), may impair maternal–fetal immune tolerance and contribute to adverse pregnancy outcomes. This study investigated the association between HLA-G promoter methylation and circulating HLA-G levels in women with unexplained RPL. METHODS AND
resultsA case–control study was conducted including 100 women with unexplained RPL and 100 age- and matched healthy parous controls. Bisulfite-treated DNA was analyzed for HLA-G promoter methylation using methylation-specific PCR, while plasma HLA-G concentrations were quantified by ELISA. Statistical analyses included group comparisons, correlation analysis, and receiver operating characteristic (ROC) curve analysis. Women with RPL exhibited significantly lower plasma HLA-G levels compared with controls (97.3 ± 19.0 vs. 106.1 ± 10.3; p < 0.05). The frequency of methylated HLA-G promoter alleles was significantly higher in the RPL group (62%) than in controls (24%) (p < 0.05). A modest but significant inverse association was observed between HLA-G promoter methylation and plasma HLA-G levels (p = 0.010). ROC analysis demonstrated high specificity (97%) but limited sensitivity (48%), with a low area under the curve (AUC = 0.348).
conclusionIncreased HLA-G promoter methylation and reduced circulating HLA-G levels are associated with recurrent pregnancy loss, supporting a contributory role of epigenetic regulation in RPL. However, HLA-G promoter methylation alone shows limited predictive utility and may be more informative when integrated with additional molecular or clinical markers.
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