Background
Studies have shown that the effects of maternal nutrition exposure during gestation influence metabolic risk in early life through an epigenetic mechanism. Low glycaemic index (GI) diets benefit both maternal and neonatal gestational outcomes. We hypothesize that maternal dietary GI or glycaemic load (GL) changes during pregnancy impact placental DNA methylation, especially in insulin resistance-related genes.
Methods
From a clinical trial of overweight pregnant women, 12 subjects who successfully reduced their GI and another 12 whose GI increased despite the intervention were selected. A genome-wide differential methylation analysis of placental tissue DNA was conducted, followed by bioinformatic annotation and validation analysis. The distribution of genome-wide differentially methylated regions (DMRs) and CpG sites was described. Six CpG sites in regulatory regions of four insulin-related genes (
PLIN1
,
CPT1B
,
SSTR4
, and
CIDEA
) were selectively validated by pyrosequencing. Pairwise Spearman correlation analysis was performed to test methylation–phenotype association in an additional 153 subjects from the same trial. Correlation between methylation of significant sites and placental mRNA expression of
SSTR4
was also analysed.
Results
Dietary GI decreased by 24.3 (26.2–20.1) in the group who responded appropriately to the intervention and increased by 19.6 (15.2–29.1) in the comparison group. Epigenome-wide analysis identified 108 DMRs and 365 CpG sites with
P
< 0.05 adjusted by false discovery rate, distributed over all chromosomes. The methylation level of cg05009389 in the 3′ UTR of
PLIN1
was negatively correlated with maternal weight gain (
ρ
= − 0.21,
P
= 0.027) and increase in insulin levels (
ρ
= − 0.24,
P
= 0.015) during gestation. Methylation levels of cg17586860 and cg18197392 in the 5′ UTR region of
SSTR4
were negatively correlated with changes in dietary carbohydrate intake (
ρ
= − 0.24,
P
s ≤ 0.006) and GL across gestation (
ρ
= − 0.23,
P
s ≤ .008). This correlation survived the adjustment for maternal factors such as dietary GI, body mass index, and gestational diabetes. Up to 89% of cg18197392 methylation was explained by GL change. Cg14631053 methylation correlated positively with mRNA expression of
SSTR4
in the placenta (
ρ
= 0.20,
P
= 0.037)
.
Conclusions
We provide the first evidence that maternal dietary GI changes during gestation may impact placental DNA...
To provide a current estimation of overweight, gestational weight gain(GWG), elevated fasting plasma glucose (FPG) in pregnant women in Kunshan, China and investigate their association with macrosomia using recommendations of IOM and International Association of Diabetes and Pregnancy Study Groups. We conducted a population-based retrospective study and analyzed routine data from Kunshan Maternity and Child Care Surveillance System of 27,322 women with singleton full-term birth from 2006 to 2010. The prevalence of maternal overweight at early pregnancy according to WHO BMI categories (BMI: 25.0-29.9 kg/m(2)) or the cutoffs for Chinese (BMI:24.0-27.9 kg/m(2)), elevated FPG (≥5.1 mmol/L) were estimated. Proportions of women with GWG below, within and above 2009 IOM recommendations were used to evaluate the adequacy of GWG. The association between maternal overweight, GWG, elevated FPG and macrosomia was analyzed by multiple logistic regression. The prevalence of maternal overweight was 8.9 % according to WHO BMI categories and 11.9 % according to Chinese cutoffs. The rate of elevated FPG at first prenatal visit was 19.4 %. Overweight women gained, on average, 12.2 ± 5.3 or 13.0 ± 5.2 (kg) during gestation, 57.1 or 63.93 % of which had excessive weight gain above IOM recommendations (6.8-11.4 kg) according to WHO BMI categories or Chinese cutoffs, respectively. Maternal overweight, GWG and elevated FPG were positively and significantly associated with macrosomia after adjusting for maternal age and gestational weeks at delivery. Maternal overweight, excessive weight gain, elevated FPG are common in the Chinese population in Kunshan. These metabolic risk factors associated with macrosomia should be controlled under the recommendations for Chinese pregnant population.
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