Maternal genome-wide DNA methylation patterns and congenital heart defects.
Maternal genome-wide DNA methylation patterns and congenital heart defects.
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DOI：
10.1371/journal.pone.0016506
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发表时间：
2011-01-24
期刊：
影响因子：
3.7
通讯作者：
Hobbs CA
中科院分区：
文献类型：
--
作者：
Chowdhury S;Erickson SW;MacLeod SL;Cleves MA;Hu P;Karim MA;Hobbs CA
大多数先天性心脏病（CHD）被认为是多种遗传、表观遗传、环境和生活方式因素相互作用的结果。表观遗传机制是复杂疾病研究中有吸引力的目标，因为它们可能会被环境因素和饮食干预所改变。我们进行了一项基于人群的全基因组母体DNA甲基化病例对照研究，以确定基因特异性甲基化的改变是否与CHD相关。使用Illumina Infinium Human Methylation 27 BeadChip，我们评估了从外周血淋巴细胞分离的DNA中超过27，000个CpG位点的母体基因特异性甲基化。我们的研究样本包括180名非综合征CHD影响妊娠的母亲（病例）和187名未受影响妊娠的母亲（对照）。使用多因子统计模型，我们观察到在多个CpG位点的病例和对照之间的差异甲基化，尽管没有CpG位点达到全基因组统计学显著性的最严格水平。大多数差异甲基化的CpG位点在病例中是高甲基化的，并且位于CpG岛内。基因集富集分析（GSEA）显示，感兴趣的基因富集在涉及胎儿发育的多个生物学过程。还观察到与先前显示参与胎儿器官发生的典型途径的关联。我们提出的初步证据表明，母体DNA甲基化的改变可能与CHD有关。我们的研究结果表明，进一步的研究，涉及产妇表观遗传模式和冠心病是必要的。已经确定了未来研究的多个候选过程和途径。
The majority of congenital heart defects (CHDs) are thought to result from the interaction between multiple genetic, epigenetic, environmental, and lifestyle factors. Epigenetic mechanisms are attractive targets in the study of complex diseases because they may be altered by environmental factors and dietary interventions. We conducted a population based, case-control study of genome-wide maternal DNA methylation to determine if alterations in gene-specific methylation were associated with CHDs. Using the Illumina Infinium Human Methylation27 BeadChip, we assessed maternal gene-specific methylation in over 27,000 CpG sites from DNA isolated from peripheral blood lymphocytes. Our study sample included 180 mothers with non-syndromic CHD-affected pregnancies (cases) and 187 mothers with unaffected pregnancies (controls). Using a multi-factorial statistical model, we observed differential methylation between cases and controls at multiple CpG sites, although no CpG site reached the most stringent level of genome-wide statistical significance. The majority of differentially methylated CpG sites were hypermethylated in cases and located within CpG islands. Gene Set Enrichment Analysis (GSEA) revealed that the genes of interest were enriched in multiple biological processes involved in fetal development. Associations with canonical pathways previously shown to be involved in fetal organogenesis were also observed. We present preliminary evidence that alterations in maternal DNA methylation may be associated with CHDs. Our results suggest that further studies involving maternal epigenetic patterns and CHDs are warranted. Multiple candidate processes and pathways for future study have been identified.
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DOI：
10.1007/s00428-009-0847-2
发表时间：
2010-01
期刊：
Virchows Archiv : an international journal of pathology
影响因子：
--
作者：
Feinberg AP
通讯作者：
Feinberg AP
DOI：
10.1002/bdra.20670
发表时间：
2010-07-01
影响因子：
--
作者：
Chen, Xiaoli;Guo, Jin;Zhang, Ting
通讯作者：
Zhang, Ting
影响因子：
2.7
作者：
Bell CG;Teschendorff AE;Rakyan VK;Maxwell AP;Beck S;Savage DA
通讯作者：
Savage DA
DOI：
10.1073/pnas.0703739104
发表时间：
2007-08-07
影响因子：
11.1
作者：
Dolinoy, Dana C.;Huang, Dale;Jirtle, Randy L.
通讯作者：
Jirtle, Randy L.
影响因子：
120.7
作者：
Bjornsson, Hans T.;Sigurdsson, Martin I.;Feinberg, Andrew P.
通讯作者：
Feinberg, Andrew P.