Maternal obesity linked to altered DNA methylation of iron-regulating genes in early pregnancy
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Key Takeaway
Note preliminary link between maternal obesity and altered iron gene methylation in early pregnancy.
This cross-sectional study analyzed data from a double-blind randomized controlled trial, examining 65 singleton pregnant women at 12 gestational weeks (34 normal weight, 31 obesity). It compared maternal adiposity (BMI, fat mass, visceral fat) between groups, assessing DNA methylation of TfR2 and HJV genes as the primary outcome, with inflammatory and iron status markers as secondary outcomes.
Key results showed lower DNA methylation at specific TfR2 CpG sites in women with obesity. Mean TfR2z1 methylation was 5.80% in obesity versus 6.92% in normal weight (P = 0.004). For TfR2z2, CpG 5 methylation was 12.5% vs 14.7% (P = 0.035), and CpG 6 was 17.8% vs 20.1% (P = 0.031). Conversely, HJV gene methylation was higher in obesity: HJVz1 CpG 3 was 45.3% vs 43.4% (P = 0.010), and HJVz2 CpG 2 was 43.2% vs 37.9% (P < 0.001). Mean HJVz2 methylation was 65.9% vs 61.6% (P < 0.001).
Safety and tolerability were not reported. Key limitations include the small sample size, cross-sectional design preventing causal inference, lack of reported effect sizes, and unknown clinical significance of the methylation changes. The setting and follow-up duration were also not reported.
For practice, this early-stage, mechanistic research identifies a potential epigenetic link between maternal obesity and fetal iron regulation. Clinicians should interpret these findings as hypothesis-generating. They do not support changes to clinical management but highlight an area for further longitudinal investigation.
View Original Abstract ↓
BACKGROUND: Growing evidence shows that obesity influences iron status during pregnancy; however, it is unknown whether maternal obesity is associated with epigenetic changes in transferrin receptor 2 (TfR2) and hemojuvelin (HJV).
OBJECTIVES: This study aimed to explore the association between adiposity and DNA methylation in TfR2 and HJV in early pregnancy and the mediating effect of inflammation on this association.
METHODS: This cross-sectional study used data from a double-blind randomized controlled trial in singleton pregnant women with normal weight (BMI: 18.5-24.9 kg/m) and obesity (BMI: ≥30.0 kg/m). Maternal BMI, fat mass, visceral fat, iron/inflammatory markers and DNA methylation of TfR2 and HJV were measured at 12 gestational weeks. Two primer sets were designed [TfR2 zone 1 and 2 (TfR2z1, TfR2z2); HJV zone 1 and 2 (HJVz1, HJVz2)]. An inflammation score was calculated using proinflammatory cytokines.
RESULTS: A total of 65 pregnant women were included, 34 with normal weight, and 31 with obesity. Compared to women of normal-weight, those with obesity showed: lower percentage DNA methylationat TfR2z1 cytosine-phosphate-guanine (CpG) sites 5, 6, 8-10 and the mean TfR2z1 methylation (mean TfR2z1 methylation 5.80% vs 6.92%, P = 0.004); lower percentage of DNA methylation at TfR2z2 CpG sites 5 and 6 (12.5% vs 14.7%, P = 0.035; 17.8% vs 20.1%, P = 0.031); higher percentage DNA methylation at HJVz1 CpG site 3 (HJVz1 CpG 3 45.3% vs 43.4%, P = 0.010) and HJVz2 CpG site 2 and the mean HJVz2 methylation (HJVz2 CpG 2 43.2% vs 37.9%, P < 0.001, mean HJVz2 methylation 65.9% vs 61.6%, P < 0.001). Adjusting for covariates, DNA methylation at TfR2z1 was negatively and HJVz2 positively associated with all adiposity measures (TfR2z1, BMI β = -0.288, P = 0.030; HJVz2 β = 0.459, P < 0.001). Inflammation showed a mediating effect on the association between all adiposity measures and DNA methylation at HJVz1 (P = 0.019).
CONCLUSIONS: Maternal adiposity is associated with epigenetic alterations in the iron metabolism genes TfR2 and HJV in early pregnancy, with modifications in HJV appearing to be mediated by inflammatory pathways.
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