Prenatal famine and genetic variation are independently and additively associated with DNA methylation at regulatory loci within IGF2/H19.
Prenatal famine and genetic variation are independently and additively associated with DNA methylation at regulatory loci within IGF2/H19.
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DOI：
10.1371/journal.pone.0037933
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lumey LH
中科院分区：
文献类型：
--
作者：
Tobi EW;Slagboom PE;van Dongen J;Kremer D;Stein AD;Putter H;Heijmans BT;Lumey LH
早期环境和遗传变异都可能影响DNA甲基化，这是表观基因组的主要分子标记之一。到目前为止，这些因素对一个明确的基因座的综合影响尚未得到研究。作为早期环境暴露的一个例子，我们评估了1944-45年荷兰饥荒的妊娠暴露与印迹IGF2/H19区域DNA甲基化的单核苷酸多态性（标记snp）之间的关系，这是一个表观遗传调控的基因组区域模型。在调节IGF2/H19区域印迹状态的5个差异甲基化区（DMRs）测量DNA甲基化。将60名孕前饥荒暴露者与未暴露的同性兄弟姐妹进行比较，观察到DNA甲基化在所有IGF2 DMR上存在微小但一致的差异（经多次测试调整后PBH<0.05），但在H19 DMR上没有差异。IGF2 DMR0甲基化与IGF2 SNP rs2239681相关（PBH = 0.027）， INS启动子甲基化与INS SNP相关，包括标记INS VNTR的rs689，这提示了VNTR对INS表达影响的机制（PBH = 3.4×10−3）。产前饥荒和遗传变异与IGF2/H19甲基化有相似的关联，且它们的贡献是加性的。它们的绝对值很小（<3%），但相对于总体的变化平均为0.5个标准差。我们的分析表明，环境和遗传因素可能在相同的调控位点上对DNA甲基化产生独立和附加的类似大小的影响。
Both the early environment and genetic variation may affect DNA methylation, which is one of the major molecular marks of the epigenome. The combined effect of these factors on a well-defined locus has not been studied to date. We evaluated the association of periconceptional exposure to the Dutch Famine of 1944–45, as an example of an early environmental exposure, and single nucleotide polymorphisms covering the genetic variation (tagging SNPs) with DNA methylation at the imprinted IGF2/H19 region, a model for an epigenetically regulated genomic region. DNA methylation was measured at five differentially methylated regions (DMRs) that regulate the imprinted status of the IGF2/H19 region. Small but consistent differences in DNA methylation were observed comparing 60 individuals with periconceptional famine exposure with unexposed same-sex siblings at all IGF2 DMRs (PBH<0.05 after adjustment for multiple testing), but not at the H19 DMR. IGF2 DMR0 methylation was associated with IGF2 SNP rs2239681 (PBH = 0.027) and INS promoter methylation with INS SNPs, including rs689, which tags the INS VNTR, suggesting a mechanism for the reported effect of the VNTR on INS expression (PBH = 3.4×10−3). Prenatal famine and genetic variation showed similar associations with IGF2/H19 methylation and their contributions were additive. They were small in absolute terms (<3%), but on average 0.5 standard deviations relative to the variation in the population. Our analyses suggest that environmental and genetic factors could have independent and additive similarly sized effects on DNA methylation at the same regulatory site.
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影响因子：
64.5
作者：
Carone BR;Fauquier L;Habib N;Shea JM;Hart CE;Li R;Bock C;Li C;Gu H;Zamore PD;Meissner A;Weng Z;Hofmann HA;Friedman N;Rando OJ
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作者：
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56.9
作者：
Cui, HM;Cruz-Correa, M;Feinberg, AP
通讯作者：
Feinberg, AP