Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels
Mediation Analysis Supports a Causal Relationship between Maternal Hyperglycemia and Placental DNA Methylation Variations at the Leptin Gene Locus and Cord Blood Leptin Levels
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DOI：
10.3390/ijms21010329
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发表时间：
2020-01-01
影响因子：
5.6
通讯作者：
Bouchard, Luigi
中科院分区：
文献类型：
--
作者：
Gagne-Ouellet, Valerie;Breton, Edith;Bouchard, Luigi
胎儿瘦素 (LEP) 基因 DNA 甲基化 (DNAm) 的变化与母亲高血糖有关，但其与儿童肥胖风险的关系仍不清楚。我们在 259 名母婴中调查了 3 岁时母亲高血糖、胎盘 LEP DNAm（25 5 '-C-磷酸盐-G-3' (CpG) 位点）、新生儿瘦素血症和肥胖（即 BMI 和皮褶厚度 (ST)（肩胛下 (SS) + 三头肌 (TR) 皮褶测量，以及 SS:TR 比率）之间的关联我们针对出生胎龄、儿童性别、随访年龄和细胞异质性进行了多变量线性分析，并使用中介分析评估了 DNAm 在母亲血糖与儿童结局之间的因果关系。
Changes in fetal DNA methylation (DNAm) of the leptin (LEP) gene have been associated with exposure to maternal hyperglycemia, but their links with childhood obesity risk are still unclear. We investigated the association between maternal hyperglycemia, placental LEP DNAm (25 5 '-C-phosphate-G-3 ' (CpG) sites), neonatal leptinemia, and adiposity (i.e., BMI and skinfold thickness (ST) (subscapular (SS) + triceps (TR) skinfold measures, and the ratio of SS:TR) at 3-years-old, in 259 mother-child dyads, from Gen3G birth cohort. We conducted multivariate linear analyses adjusted for gestational age at birth, sex of the child, age at follow-up, and cellular heterogeneity. We assessed the causal role of DNAm in the association between maternal glycemia and childhood outcomes, using mediation analysis. We found three CpGs associated with neonatal leptinemia (p