Gagné-Ouellet Valérie, Houde Andrée-Anne, Guay Simon-Pierre, Perron Patrice, Gaudet Daniel, Guérin Renée, Jean-Patrice Baillargeon, Hivert Marie-France, Brisson Diane, Bouchard Luigi
a Department of Biochemistry , Université de Sherbrooke , Sherbrooke , QC , Canada.
b ECOGENE-21 Biocluster , Chicoutimi , Quebec , Canada , QC , Canada.
Epigenetics. 2017 Aug;12(8):616-625. doi: 10.1080/15592294.2017.1322254. Epub 2017 May 9.
Gestational diabetes mellitus (GDM) is associated with obesity in childhood. This suggests that consequences of in utero exposure to maternal hyperglycemia extend beyond the fetal development, possibly through epigenetic programming. The aims of this study were to assess whether placental DNA methylation (DNAm) marks were associated with maternal GDM status and to offspring body composition at 5 years old in a prospective birth cohort. DNAm levels were measured in the fetal side of the placenta in 66 samples (24 from GDM mothers) using bisDNA-pyrosequencing. Anthropometric and body composition (bioimpedance) were measured in children at 5 years of age. Mann-Whitney and Spearman tests were used to assess associations between GDM, placental DNAm levels at the lipoprotein lipase (LPL) locus and children's weight, height, body mass index (BMI), body fat, and lean masses at 5 years of age. Weight, height, and BMI z-scores were computed according to the World Health Organization growth chart. Analyses were adjusted for gestational age at birth, child sex, maternal age, and pre-pregnancy BMI. LPL DNAm levels were positively correlated with birth weight z-scores (r = 0.252, P = 0.04), and with mid-childhood weight z-scores (r = 0.314, P = 0.01) and fat mass (r = 0.275, P = 0.04), and negatively correlated with lean mass (r = -0.306, P = 0.02). We found a negative correlation between LPL DNAm and mRNA levels in placenta (r = -0.459; P < 0.001), which highlights the regulation of transcriptional activity by these epivariations. We demonstrated that alterations in fetal placental DNAm levels at the LPL gene locus are associated with the anthropometric profile in children at 5 years of age. These findings support the concept of fetal metabolic programming through epigenetic changes.
妊娠期糖尿病（GDM）与儿童肥胖有关。这表明子宫内暴露于母体高血糖的后果不仅限于胎儿发育，可能还通过表观遗传编程产生影响。本研究的目的是在一个前瞻性出生队列中评估胎盘DNA甲基化（DNAm）标记是否与母体GDM状态以及5岁后代的身体组成相关。使用双脱氧核苷酸焦磷酸测序法在66个样本（24个来自GDM母亲）的胎盘胎儿侧测量DNAm水平。在5岁儿童中测量人体测量学指标和身体组成（生物电阻抗）。使用曼-惠特尼检验和斯皮尔曼检验评估GDM、脂蛋白脂肪酶（LPL）基因座处的胎盘DNAm水平与5岁儿童的体重、身高、体重指数（BMI）、体脂和瘦体重之间的关联。根据世界卫生组织生长图表计算体重、身高和BMI z评分。分析对出生时的胎龄、儿童性别、母亲年龄和孕前BMI进行了校正。LPL DNAm水平与出生体重z评分呈正相关（r = 0.252，P = 0.04），与儿童中期体重z评分呈正相关（r = 0.314，P = 0.01）以及与脂肪量呈正相关（r = 0.275，P = 0.04），与瘦体重呈负相关（r = -0.306，P = 0.02）。我们发现胎盘LPL DNAm与mRNA水平之间存在负相关（r = -0.459；P < 0.001），这突出了这些表观变异对转录活性的调节作用。我们证明，LPL基因座处胎儿胎盘DNAm水平的改变与5岁儿童的人体测量学特征相关。这些发现支持了通过表观遗传变化进行胎儿代谢编程的概念。
