Altered HDAC expression is associated with CYP24A1-mediated vitamin D deficiency in gestational diabetes mellitus.

BACKGROUND

Low vitamin D levels during pregnancy are associated with an increased risk of Gestational Diabetes Mellitus (GDM), potentially mediated by altered vitamin D metabolism. Cytochrome P450 family 24 subfamily A member 1 (CYP24A1) plays a key role in vitamin D catabolism, but its epigenetic regulation in GDM remains unclear.

RESEARCH DESIGN AND

METHODS

This cross-sectional study included 150 pregnant women [normoglycemic (NGDM, n = 50), early GDM (eGDM, n = 50), and GDM (n = 50)] and 40 placental samples (NGDM, n = 20; GDM, n = 20). Gene expression of histone deacetylases (HDACs), sirtuins (SIRTs), and CYP24A1 was analyzed using real-time PCR. In vitro experiments using BeWo cells assessed the effects of high glucose and trichostatin A (TSA).

RESULTS

CYP24A1 expression was significantly increased in GDM participants. Distinct alterations in HDAC and SIRT expression were observed, with HDAC3, HDAC4, and HDAC7 negatively correlated and SIRT7 positively correlated with CYP24A1. HDAC modulation using TSA regulated CYP24A1 expression under hyperglycemic conditions.

CONCLUSIONS

These findings offer insights into the association of multiple HDACs regulating CYP24A1-mediated vitamin D deficiency in the pathophysiology of GDM. However, further mechanistic and longitudinal studies are required to elucidate the precise mechanism.