Gene-specific DNA methylation in newborns in response to folic acid supplementation during the second and third trimesters of pregnancy: epigenetic analysis from a randomized controlled trial
Gene-specific DNA methylation in newborns in response to folic acid supplementation during the second and third trimesters of pregnancy: epigenetic analysis from a randomized controlled trial
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DOI：
10.1093/ajcn/nqx069
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发表时间：
2018-04-01
影响因子：
7.1
通讯作者：
Pentieva, Kristina
中科院分区：
文献类型：
--
作者：
Caffrey, Aoife;Irwin, Rachelle E.;Pentieva, Kristina
新出现的证据表明，母亲的叶酸水平会影响儿童的认知发育。叶酸依赖的DNA甲基化可能提供了一种生物学机制，将妊娠期间叶酸状态与后代的认知能力联系起来。本研究的目的是研究妊娠早期继续补充叶酸（FA）对脐带血中与脑发育和功能相关的表观遗传学控制基因DNA甲基化的影响。使用现有的脐带血样本（n = 86）从妊娠中期和晚期叶酸补充（FASSTT）试验中，我们应用焦磷酸测序技术分析了9个已知受甲基化调控的候选基因座的脐带血DNA，包括一些先前在观察性研究中涉及的基因座：广泛分布的反转录转座子长散布核元件-1（LINE-1）和8个单拷贝位点（RBM46、PEG 3、IGF 2、GRB 10、BDNF、GRIN 3B、OPCML和APC 2）。（400 μ g/d）通过第二和第三孕期，与安慰剂相比，在LINE-1中，（56.3% +/- 1.7%对比57.2% +/- 2.1%;P = 0.024），IFG 2（48.9% +/- 4.4%对比51.2% +/- 5.1%;P = 0.021）和BDNF（2.7% +/- 0.7%对比3.1% +/- 0.8%;P = 0.003）。FA处理对DNA甲基化的影响仅在雌性后代中对IGF 2有显著性影响（P = 0.028），仅在雄性后代中对BDNF有显著性影响（P = 0.012）。对于GRB 10和GRIN 3B，我们没有发现对整体甲基化的影响;然而，个别胞嘧啶磷酸鸟嘌呤位点显示出显着的DNA甲基化变化，以响应FA。继续补充FA通过妊娠2和3个月的结果在脐带血中的DNA甲基化的显着变化与大脑发育相关的基因。这些发现提供了一种潜在的生物学机制，将母体叶酸状态与后代的神经发育联系起来，但这需要使用全基因组方法进行进一步研究。www.isrctn.com
Emerging evidence suggests that maternal folate status can impact cognitive development in childhood. Folate-dependent DNA methylation may provide a biological mechanism to link folate status during pregnancy with cognition in the offspring.The objective was to investigate the effect of continued folic acid (FA) supplementation beyond the first trimester of pregnancy on DNA methylation in cord blood of epigenetically controlled genes related to brain development and function.Using available cord blood samples (n = 86) from the Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) trial in pregnancy, we applied pyrosequencing techniques to analyze cord blood DNA at 9 candidate loci known to be regulated by methylation, including some previously implicated in observational studies: the widely dispersed retrotransposon long interspersed nuclear element-1 (LINE-1) and 8 single-copy loci (RBM46, PEG3, IGF2, GRB10, BDNF, GRIN3B, OPCML, andAPC2).The newborns of mothers who received ongoing FA (400 A mu g/d) through the second and third trimesters, compared with placebo, had significantly lower overall DNA methylation levels at LINE-1 (56.3% +/- 1.7% compared with 57.2% +/- 2.1%;P = 0.024),IFG2 (48.9% +/- 4.4% compared with 51.2% +/- 5.1%;P = 0.021), andBDNF (2.7% +/- 0.7% compared with 3.1% +/- 0.8%;P = 0.003). The effect of FA treatment on DNA methylation was significant only in female offspring forIGF2 (P = 0.028) and only in males forBDNF (P = 0.012). ForGRB10 andGRIN3B, we detected no effect on overall methylation; however, individual cytosine-phosphate-guanine sites showed significant DNA methylation changes in response to FA.Continued supplementation with FA through trimesters 2 and 3 of pregnancy results in significant changes in DNA methylation in cord blood of genes related to brain development. The findings offer a potential biological mechanism linking maternal folate status with neurodevelopment of the offspring, but this requires further investigation using a genome-wide approach.This trial was registered at www.isrctn.com as ISRCTN19917787.