Offspring DNA methylation of the aryl-hydrocarbon receptor repressor gene is associated with maternal BMI, gestational age, and birth weight
Offspring DNA methylation of the aryl-hydrocarbon receptor repressor gene is associated with maternal BMI, gestational age, and birth weight
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DOI：
10.1080/15592294.2015.1078963
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发表时间：
2015-10-03
期刊：
影响因子：
3.7
通讯作者：
Tellez-Rojo, Martha M.
中科院分区：
文献类型：
--
作者：
Burris, Heather H.;Baccarelli, Andrea A.;Tellez-Rojo, Martha M.
产前烟雾暴露、母亲肥胖、胎儿生长异常和早产都是后代代谢综合征的危险因素。脐带血芳基烃受体阻遏物 (AHRR) DNA 甲基化对母亲怀孕期间吸烟有反应。 AHRR 不仅可以抑制参与介导异生物质代谢的芳基烃受体 (AHR) 转录，而且还参与细胞生长和分化。除了母亲吸烟之外，后代 AHRR DNA 甲基化状态的其他预测因素仍然未知。我们试图在新生儿中识别出它们。我们将孕妇纳入墨西哥城的 PROGRESS 出生队列。使用焦磷酸测序，我们分析了 531 名婴儿脐带血中 AHRR 基因启动子内 3CpG 位点的 DNA 甲基化。我们使用广义估计方程来解释 CpG 位点之间 DNA 甲基化的相关性。使用多变量模型来调整母亲年龄、BMI、教育程度、产次、烟雾暴露、婴儿性别、胎龄和出生胎龄体重。 AHRR DNA 甲基化与母亲 BMI (P = 0.0009) 呈正相关，与妊娠长度 (P < 0.0001) 和出生胎龄体重 (P < 0.0001) 呈负相关。与正常体重母亲相比，肥胖母亲的后代 AHRR DNA 甲基化水平高出 2.1%，早产儿与足月婴儿的 AHRR DNA 甲基化水平高出 3.1%，分别代表甲基化水平的三分之一和二分之一标准差差异。总之，后代 AHRR DNA 甲基化与母亲怀孕期间的肥胖以及婴儿胎龄和出生胎龄体重相关。需要进一步开展工作来发现 AHRR DNA 甲基化改变对健康的影响。
Prenatal smoke exposure, maternal obesity, aberrant fetal growth, and preterm birth are all risk factors for offspring metabolic syndrome. Cord blood aryl-hydrocarbon receptor repressor (AHRR) DNA methylation is responsive to maternal smoking during pregnancy. AHRR serves not only to inhibit aryl-hydrocarbon receptor (AHR) transcription, which is involved in mediating xenobiotic metabolism, but it is also involved in cell growth and differentiation. Other than maternal smoking, other predictors of offspring AHRR DNA methylation status remain unknown; we sought to identify them among newborns. We enrolled pregnant women in the PROGRESS birth cohort in Mexico City. Using pyrosequencing, we analyzed DNA methylation of 3CpG sites within the AHRR gene promoter from the umbilical cord blood of 531 infants. We used generalized estimating equations to account for the correlation of DNA methylation between CpG sites. Multivariable models were used to adjust for maternal age, BMI, education, parity, smoke-exposure, infant sex, gestational age, and birth weight-for-gestational age. AHRR DNA methylation was positively associated with maternal BMI (P = 0.0009) and negatively associated with the length of gestation (P < 0.0001) and birth weight-for-gestational age (P < 0.0001). AHRR DNA methylation was 2.1% higher in offspring of obese vs. normal weight mothers and 3.1% higher in preterm vs. term infants, representing a third and a half standard deviation differences in methylation, respectively. In conclusion, offspring AHRR DNA methylation was associated with maternal obesity during pregnancy as well as infant gestational age and birth weight-for-gestational age. Further work to discover the health impacts of altered AHRR DNA methylation is warranted.