Reduced DNA methylation at the PEG3 DMR and KvDMR1 loci in children exposed to alcohol in utero: a South African Fetal Alcohol Syndrome cohort study.
Reduced DNA methylation at the PEG3 DMR and KvDMR1 loci in children exposed to alcohol in utero: a South African Fetal Alcohol Syndrome cohort study.
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DOI：
10.3389/fgene.2015.00085
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发表时间：
2015
影响因子：
3.7
通讯作者：
Ramsay M
中科院分区：
文献类型：
--
作者：
Masemola ML;van der Merwe L;Lombard Z;Viljoen D;Ramsay M
胎儿酒精综合征(Fas)是胎儿发育过程中酒精暴露所致的一种破坏性发育障碍。它是一个相当大的全球公共卫生问题，以中枢神经系统异常、面部畸形和生长迟缓为特征。印记基因在植物的生长发育中起着重要的作用，因此我们研究了四个印记控制区：H19ICR、IG-DMR、KvDMR1和Peg3DMR。有人提出，DNA甲基化的变化可能导致在Fas中出现的发育异常，并持续到成年。参与者包括来自西开普省和北开普省的Fas儿童和对照组。从血液和口腔细胞中提取的DNA样品经亚硫酸氢盐修饰后，通过聚合酶链式反应扩增ICR，并通过焦磷酸测序得出所选CpG二核苷酸甲基化的定量估计：H19 ICR(6个CpG位点；50名对照和73例病例)；KvDMR1(7、55和86)；IG-DMR(10、56和84)；以及Peg3 DMR(7、50和79)。酒精暴露对神经元发育的影响最深远。在这项研究中，我们报告了在血液中观察到的表观遗传效应，这种效应可能不直接反映发育中的大脑的组织特异性变化。在调整了年龄和性别(已知的DNA甲基化混杂因素)后，KvDMR1和PEG3DMR有显著差异，但H19ICR没有显著差异，在IG-DMR只有很小的影响(在病例中降低了0.84%；p=0.035)。两个母系印记基因座KvDMR1和Peg3DMR在Fas病例中的平均甲基化水平较低(分别为1.49%和7.09%；P<；0.001和0.001)。最大的影响是在Peg3 DMR，尽管功能影响尚不确定。这项研究支持表观遗传调节作为酒精致畸效应的一种机制，通过改变印记基因座的甲基化特征以一种特定的方式。
Fetal alcohol syndrome (FAS) is a devastating developmental disorder resulting from alcohol exposure during fetal development. It is a considerable public health problem worldwide and is characterized by central nervous system abnormalities, dysmorphic facial features, and growth retardation. Imprinted genes are known to play an important role in growth and development and therefore four imprinting control regions (ICRs), H19 ICR, IG-DMR, KvDMR1 and PEG3 DMR were examined. It is proposed that DNA methylation changes may contribute to developmental abnormalities seen in FAS and which persist into adulthood. The participants included FAS children and controls from the Western and Northern Cape Provinces. DNA samples extracted from blood and buccal cells were bisulfite modified, the ICRs were amplified by PCR and pyrosequencing was used to derive a quantitative estimate of methylation at selected CpG dinucleotides: H19 ICR (six CpG sites; 50 controls and 73 cases); KvDMR1 (7, 55, and 86); IG-DMR (10, 56, and 84); and PEG3 DMR (7, 50, and 79). The most profound effects of alcohol exposure are on neuronal development. In this study we report on epigenetic effects observed in blood which may not directly reflect tissue-specific alterations in the developing brain. After adjusting for age and sex (known confounders for DNA methylation), there was a significant difference at KvDMR1 and PEG3 DMR, but not the H19 ICR, with only a small effect (0.84% lower in cases; p = 0.035) at IG-DMR. The two maternally imprinted loci, KvDMR1 and PEG3 DMR, showed lower average locus-wide methylation in the FAS cases (1.49%; p < 0.001 and 7.09%; p < 0.001, respectively). The largest effect was at the PEG3 DMR though the functional impact is uncertain. This study supports the role of epigenetic modulation as a mechanism for the teratogenic effects of alcohol by altering the methylation profiles of imprinted loci in a locus-specific manner.
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影响因子：
30.8
作者：
Gicquel, C;Rossignol, S;Le Bouc, Y
通讯作者：
Le Bouc, Y
产前酒精暴露后小鼠 Igf2 基因座 DNA 甲基化和基因表达略有下降：甲基补充饮食的影响。
影响因子：
2.3
作者：
Downing, Chris;Johnson, Thomas E.;Larson, Colin;Leakey, Tatiana I.;Siegfried, Rachel N.;Rafferty, Tonya M.;Cooney, Craig A.
通讯作者：
Cooney, Craig A.
影响因子：
4
作者：
Diaz-Meyer, N;Day, CD;Higgins, MJ
通讯作者：
Higgins, MJ
影响因子：
2.7
作者：
Colella, S;Shen, L;Krahe, R
通讯作者：
Krahe, R
影响因子：
5.2
作者：
Boissonnas, Celine Chalas;El Abdalaoui, Hafida;Jammes, Helene
通讯作者：
Jammes, Helene