Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1.
Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1.
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DOI：
10.1038/tp.2016.95
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发表时间：
2016-06-07
影响因子：
6.8
通讯作者：
Sonuga-Barke EJ
中科院分区：
文献类型：
--
作者：
Kumsta R;Marzi SJ;Viana J;Dempster EL;Crawford B;Rutter M;Mill J;Sonuga-Barke EJ
在整个生命周期中，包括机构剥夺和严重的童年滥用的不利环境与精神和身体健康问题的风险增加有关，尽管介导的这些效果的机制尚不清楚，但在啮齿动物模型中，最近的工作表明，表观遗传过程可能涉及严重的早期剥夺。罗马尼亚共产主义时代的孤儿院在罗马尼亚采用者中量化了约40万个基因组的颊细胞DNA甲基化（6-43个月; n = 16; n = 16; n = 17 = 17）控制了测试的问题的数量，我们确定了与细胞色素p450 2e1基因（CYP2E1）的启动子调节区域中的9个顺序CPG相关的差异甲基化区域（DMR）（DMR）。我们的数据表明环境侮辱早期发育过程中足够的生物学影响与持久的表观遗传变化有关，这可能反映了一种将早期广告与认知和神经生物学表型的影响联系起来的生物学机制。
Exposure to adverse rearing environments including institutional deprivation and severe childhood abuse is associated with an increased risk for mental and physical health problems across the lifespan. Although the mechanisms mediating these effects are not known, recent work in rodent models suggests that epigenetic processes may be involved. We studied the impact of severe early-life adversity on epigenetic variation in a sample of adolescents adopted from the severely depriving orphanages of the Romanian communist era in the 1980s. We quantified buccal cell DNA methylation at ~400 000 sites across the genome in Romanian adoptees exposed to either extended (6–43 months; n=16) or limited duration (<6 months; n=17) of severe early-life deprivation, in addition to a matched sample of UK adoptees (n=16) not exposed to severe deprivation. Although no probe-wise differences remained significant after controlling for the number of probes tested, we identified an exposure-associated differentially methylated region (DMR) spanning nine sequential CpG sites in the promoter-regulatory region of the cytochrome P450 2E1 gene (CYP2E1) on chromosome 10 (corrected P=2.98 × 10−5). Elevated DNA methylation across this region was also associated with deprivation-related clinical markers of impaired social cognition. Our data suggest that environmental insults of sufficient biological impact during early development are associated with long-lasting epigenetic changes, potentially reflecting a biological mechanism linking the effects of early-life adversity to cognitive and neurobiological phenotypes.