(LB02-20-25) Plasma 25(OH)D Levels Influence DNA Methylation Status of Interleukin-6 and Correlates With Gestational Age at Birth

Objectives: In this study, we sought to examine if plasma 25(OH)D status influences the level of DNAm in various genes associated with PTB (ie. IL-6, TNF-α) and if patterns predict gestational age at birth. Vitamin D has a unique immunomodulatory role in pregnancy, however the mechanism by which it impacts birth outcomes is not fully understood. Inflammatory pathways are well-studied mechanisms by which vitamin D may exert it effects and have also been linked with preterm birth (PTB; birth < 37 weeks gestation). Indeed, Vitamin D deficiency (VDD) has been linked with PTB. Recent research has shown that 25(OH)D may play an epigenetic role in preterm birth by controlling the DNA methylation (DNAm) status of various genes related to inflammation and immune response known to be involved with preterm birth.

Methods: In a retrospective case cohort study, which examined DNAm and plasma 25(OH)D levels from 51 pregnant African American women enrolled in the BIBB (Biosocial Impact on Black Births) study. Blood was collected from participants at 8-24 weeks gestation for both plasma 25(OH)D analysis and DNA extraction for methylation analysis.

Results: We used the Illumina EPIC Beadchip V1.0 to to quantify DNAm and identified differentially methylated regions on 15 specific CpG sites (those in the promoter region of the IL6 gene) to investigate associations between VDD in the plasma of pregnant women and gestational age at birth. DNAm in cg00087425 was significantly associated with gestational age (pre-term vs. term births) with an unadjusted Wilcoxon p-value of 0.0157, and that cg05265849, cg10140158, and cg20509117 were all associated with vitamin D deficiency status ( < 20 ng/mL) with Wilcoxon p-values of 0.023568, 0.004784998, and 0.021361 respectively. The average level of DNAm on all CpGs of the promotor site of IL6 were significantly correlated with gestational age at birth and plasma 25(OH)D concentration with Pearson’s correlations and p-values of (-0.3212146 – p=0.023190) and (0.3042153 – p=0.032234) respectively.

Conclusions: The results show that VDD may play an important role in DNA methylation of IL-6 and potentially contribute to PTB. Further research is needed to understand the mechanism by which 25(OH)D impacts inflammation and increase risk for PTB.

Funding Sources: National Institute of Minority Health Disparities