DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth: the generation R study.

DNA methylation of IGF2DMR and H19 is associated with fetal and infant growth: the generation R study.
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DOI:
10.1371/journal.pone.0081731
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Steegers-Theunissen RP
Steegers-Theunissen RP
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bouwland-Both MI;van Mil NH;Stolk L;Eilers PH;Verbiest MM;Heijmans BT;Tiemeier H;Hofman A;Steegers EA;Jaddoe VW;Steegers-Theunissen RP

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怀孕期间胚胎生长基因的表观遗传编程的变化似乎会影响胎儿的生长。因此,在荷兰的一项基于人群的前瞻性出生队列研究中,我们研究了胎儿和婴儿生长与IGF 2DMR、H19和MTHFR DNA甲基化之间的关系。本研究选择69例小于胎龄儿(SGA,出生体重<-2SDS)和471例对照组。通过一系列超声测量评估胎儿生长情况。从医疗记录中检索有关出生结局的信息。婴儿体重在三个月和六个月时进行评估。在从脐带白色血细胞提取的DNA中评估甲基化。使用以DNA甲基化作为因变量的线性混合模型进行分析。对照组中IGF 2DMR和H19的DNA甲基化水平中位数(90%范围)分别为53.6%(44.5-61.6)和30.0%(25.6-34.2),SGA组分别为52.0%(43.9-60.9)和30.5%(23.9-32.9)。在对照组和SGA组中发现MTHFR区域低甲基化,变异性有限,分别为2.5%(1.4-4.0)和2.4%(1.5-3.8)。SGA与较低的IGF 2DMR DNA甲基化相关(β = −1.07,95% CI −1.93; −0.21,P值= 0.015),但与H19甲基化无关。    出生后前三个月体重增加与IGF 2DMR DNA甲基化水平降低相关(β =-0.53,95% CI-0.91;-0.16,P值= 0.005)。    IGF 2/H19基因座的遗传变异与IGF 2DMR DNA甲基化相关(P值<0.05),但与H19甲基化无关。此外,我们的研究结果表明,DNA甲基化介导的遗传变异和SGA之间的关联的可能性。总之,IGF 2DMR和H19 DNA甲基化与胎儿和婴儿生长相关。
Changes in epigenetic programming of embryonic growth genes during pregnancy seem to affect fetal growth. Therefore, in a population-based prospective birth cohort in the Netherlands, we examined associations between fetal and infant growth and DNA methylation of IGF2DMR, H19 and MTHFR. For this study, we selected 69 case children born small-for-gestational age (SGA, birth weight <-2SDS) and 471 control children. Fetal growth was assessed with serial ultrasound measurements. Information on birth outcomes was retrieved from medical records. Infant weight was assessed at three and six months. Methylation was assessed in DNA extracted from umbilical cord white blood cells. Analyses were performed using linear mixed models with DNA methylation as dependent variable. The DNA methylation levels of IGF2DMR and H19 in the control group were, median (90% range), 53.6% (44.5–61.6) and 30.0% (25.6–34.2) and in the SGA group 52.0% (43.9–60.9) and 30.5% (23.9–32.9), respectively. The MTHFR region was found to be hypomethylated with limited variability in the control and SGA group, 2.5% (1.4–4.0) and 2.4% (1.5–3.8), respectively. SGA was associated with lower IGF2DMR DNA methylation (β = −1.07, 95% CI −1.93; −0.21, P-value = 0.015), but not with H19 methylation. A weight gain in the first three months after birth was associated with lower IGF2DMR DNA methylation (β = −0.53, 95% CI −0.91; −0.16, P-value = 0.005). Genetic variants in the IGF2/H19 locus were associated with IGF2DMR DNA methylation (P-value<0.05), but not with H19 methylation. Furthermore, our results suggest a possibility of mediation of DNA methylation in the association between the genetic variants and SGA. To conclude, IGF2DMR and H19 DNA methylation is associated with fetal and infant growth.
DOI: 10.1371/journal.pone.0033290
发表时间: 2012
期刊: PloS one
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作者:
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发表时间: 2012-02
期刊: The Proceedings of the Nutrition Society
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发表时间: 2012-09-01
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DOI: 10.1148/radiology.150.2.6691115
发表时间: 1984-01-01
期刊: RADIOLOGY
影响因子: 19.7
作者:
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