Arkansas Children's Nutrition Center, Little Rock, AR, USA; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Arkansas Children's Hospital, Little Rock, AR, USA.
Placenta. 2017 Sep;57:194-203. doi: 10.1016/j.placenta.2017.07.009. Epub 2017 Jul 13.
Maternal obesity (OB) and excessive gestational weight gain (GWG) are strong independent contributors that augment obesity risk in offspring. However, direct evidence of epigenetic changes associated with maternal habitus remains sparse.
We utilized Bisulfite Amplicon Sequencing (BSAS) to conduct targeted DNA methylation association analysis of maternal obesity and excessive GWG with DNA methylation of select metabolism-related and imprinted genes. Umbilical cord (UC) tissue from infants born to normal weight and overweight/obese women from the Glowing study were utilized (n = 78).
In multivariable linear regression adjusted for relevant confounders, Institute on Medicine (IOM) GWG category and infant sex were significantly associated with UC IGFBP1 methylation, while gestation length was significantly associated with UC PRKAA1 methylation. In addition, infant fat mass (%) at 2 weeks of age was significantly associated with umbilical cord methylation of RAPTOR. While regression tree analysis confirmed findings from multivariable models demonstrating that maternal early pregnancy BMI and IOM GWG category are associated with fetal UC DNA methylation patterns for select metabolic and imprinted genes, in general, effect sizes were quite small and statistical significance was not maintained when accounting for multiple testing.
Our findings suggest that maternal obesity and excessive GWG are weakly correlated with offspring DNA methylation patterns at birth.
母体肥胖（OB）和妊娠体重过度增加（GWG）是增强后代肥胖风险的两个强有力的独立因素。然而，与母体体型相关的表观遗传变化的直接证据仍然很少。
我们利用亚硫酸氢盐扩增测序（BSAS）对母体肥胖和妊娠体重过度增加与选定代谢相关和印迹基因的 DNA 甲基化进行靶向 DNA 甲基化关联分析。利用 Glowing 研究中出生于正常体重和超重/肥胖女性的婴儿脐带（UC）组织（n=78）。
在调整了相关混杂因素的多变量线性回归中，医学研究所（IOM）GWG 类别和婴儿性别与 UC IGFBP1 甲基化显著相关，而妊娠时间与 UC PRKAA1 甲基化显著相关。此外，婴儿出生后 2 周的脂肪量（%）与 RAPTOR 的脐带甲基化显著相关。尽管回归树分析证实了多变量模型的发现，表明母体早孕 BMI 和 IOM GWG 类别与胎儿 UC 代谢和印迹基因的 DNA 甲基化模式有关，但总的来说，效应大小相当小，并且在考虑到多次检验时，统计显著性并未维持。
我们的发现表明，母体肥胖和妊娠体重过度增加与出生时后代的 DNA 甲基化模式弱相关。
