PGC1α Promoter Methylation in Blood at 5-7 Years Predicts Adiposity From 9 to 14 Years (EarlyBird 50)
PGC1α Promoter Methylation in Blood at 5-7 Years Predicts Adiposity From 9 to 14 Years (EarlyBird 50)
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DOI：
10.2337/db13-0671
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发表时间：
2014-07-01
期刊：
影响因子：
7.7
通讯作者：
Burdge, Graham C.
中科院分区：
文献类型：
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作者：
Clarke-Harris, Rebecca;Wilkin, Terence J.;Burdge, Graham C.
通过表观遗传过程起作用的早期环境与心脏代谢疾病（CMD）的差异风险相关，这可以通过替代组织中的表观遗传标记来预测。然而，在与健康结果或环境暴露不同的时间点进行的这种测量可能会受到随机和环境变化的干扰。为了解决这个问题，我们分析了DNA甲基化的过氧化物酶体增殖物激活受体g辅激活因子1 α启动子血液中的40名儿童（20名男孩），每年收集5至14岁之间的焦磷酸测序。每年通过双X线吸收法测量身体成分，通过加速度计测量身体活动，并通过峰值高速年龄测量青春期时间。通过电泳迁移率变动分析研究甲基化对转录因子结合的影响。七个胞嘧啶鸟嘌呤二核苷酸（CpG）位点被确定为没有显着的时间变化或关联与白细胞群体。使用广义估计方程建模表明，四个位点的甲基化预测肥胖长达14年的性别，年龄，青春期的时间，和活动无关。一个预测位点的甲基化修饰了前脂肪形成前B细胞白血病同源框-1/同源框9复合物的结合这些发现表明，在儿童时期测量的时间稳定的CpG位点可能在预测CMD风险中具有实用性。
The early environment, acting via epigenetic processes, is associated with differential risk of cardiometabolic disease (CMD), which can be predicted by epigenetic marks in proxy tissues. However, such measurements at time points disparate from the health outcome or the environmental exposure may be confounded by intervening stochastic and environmental variation. To address this, we analyzed DNA methylation in the peroxisome proliferator-activated receptor g coactivator 1 alpha promoter in blood from 40 children (20 boys) collected annually between 5 and 14 years of age by pyrosequencing. Body composition was measured annually by dual X-ray absorptiometry, physical activity by accelerometry, and pubertal timing by age at peak high velocity. The effect of methylation on transcription factor binding was investigated by electrophoretic mobility shift assays. Seven cytosine guanine dinucleotide (CpG) loci were identified that showed no significant temporal change or association with leukocyte populations. Modeling using generalized estimating equations showed that methylation of four loci predicted adiposity up to 14 years independent of sex, age, pubertal timing, and activity. Methylation of one predictive locus modified binding of the proadipogenic pre-B-cell leukemia homeobox-1/homeobox 9 complex. These findings suggest that temporally stable CpG loci measured in childhood may have utility in predicting CMD risk.