BACKGROUND Maternal diet is an important factor in prenatal development that also has implications for disease risk later in life. The adipokine leptin is a key regulator of energy homeostasis and may be involved in the association between maternal nutrition, maternal obesity, and infant outcomes. DNA methylation of placenta genes may occur in response to exposures and may program subsequent infant development. This study examined maternal diet, placenta leptin gene DNA methylation, and neonatal growth in a sample of healthy neonates and their mothers. METHODS Mothers and their healthy neonates (N = 135) were recruited within 1-2 days following delivery at Women and Infants Hospital in Providence, RI. A structured interview was conducted to assess maternal dietary intake. Maternal pre-pregnancy weight, weight gain during pregnancy, maternal health, medications, and vitamin use were obtained from medical records. Bisulfite pyrosequencing was used to measure methylation of CpG sites in the promoter region of the placenta leptin gene and determine genotype of the leptin single nucleotide polymorphism (SNP) rs2167270, which is known to influence leptin methylation. Bivariate analyses and linear regression models were used to evaluate associations of demographics, diet, and mean leptin methylation. RESULTS Genotype was a significant predictor of placenta leptin DNA methylation (p < .01), and after controlling for this and other relevant maternal and infant covariates, lower levels of leptin methylation were significantly associated with greater intake of carbohydrates (p < .05), in particular added sugars (p < .05) and white/refined carbohydrates (p < .05). Total caloric intake was also associated with placenta leptin methylation (p < .05), however after controlling for relevant covariates, significance diminished to trend-level. There were no significant associations of placenta leptin methylation and intake of protein (p > .05) or fat (p > .05). CONCLUSION These findings underline the importance of intake of carbohydrate consumption for methylation of the placenta leptin gene. Because methylation reduces gene transcription, lower methylation may indicate a placenta response to high caloric intake and carbohydrate food that would result in higher levels of this hormone during fetal development. Further investigation of the developmental ramifications of epigenetic changes to placenta leptin methylation should be pursued.

中文翻译：

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母亲饮食与胎盘瘦素甲基化的关联。

背景技术母亲饮食是产前发育的一个重要因素，也对以后生活中的疾病风险有影响。脂肪因子瘦素是能量稳态的关键调节剂，可能与孕产妇营养、孕产妇肥胖和婴儿结局之间的关联有关。胎盘基因的 DNA 甲基化可能会因暴露而发生，并可能影响随后的婴儿发育。这项研究检查了健康新生儿及其母亲样本中的母亲饮食、胎盘瘦素基因 DNA 甲基化和新生儿生长情况。方法 在罗德岛州普罗维登斯市妇婴医院分娩后 1-2 天内招募母亲及其健康新生儿 (N = 135)。进行结构化访谈以评估母亲的饮食摄入量。从医疗记录中获取母亲孕前体重、怀孕期间体重增加、母亲健康、药物和维生素使用情况。使用亚硫酸氢盐焦磷酸测序来测量胎盘瘦素基因启动子区域中 CpG 位点的甲基化，并确定瘦素单核苷酸多态性 (SNP) rs2167270 的基因型，已知该基因会影响瘦素甲基化。使用双变量分析和线性回归模型来评估人口统计、饮食和平均瘦素甲基化之间的关联。结果 基因型是胎盘瘦素 DNA 甲基化的重要预测因素 (p < .01)，在控制该变量以及其他相关母体和婴儿协变量后，较低水平的瘦素甲基化与碳水化合物摄入量增加显着相关 (p < .05) ，特别是添加糖 (p < .05) 和白色/精制碳水化合物 (p < .05)。总热量摄入也与胎盘瘦素甲基化相关（p < .05），但是在控制相关协变量后，显着性降低至趋势水平。胎盘瘦素甲基化与蛋白质 (p > .05) 或脂肪 (p > .05) 摄入量没有显着相关性。结论 这些发现强调了碳水化合物的摄入对于胎盘瘦素基因甲基化的重要性。由于甲基化会减少基因转录，因此较低的甲基化可能表明胎盘对高热量摄入和碳水化合物食物的反应，这会导致胎儿发育过程中这种激素的水平升高。应进一步研究胎盘瘦素甲基化表观遗传变化的发育影响。