Piyasena Chinthika, Cartier Jessy, Provençal Nadine, Wiechmann Tobias, Khulan Batbayar, Sunderesan Raju, Menon Gopi, Seckl Jonathan R, Reynolds Rebecca M, Binder Elisabeth B, Drake Amanda J
British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK; Neonatal Unit, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh, UK.
British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh , Edinburgh , UK.
Front Endocrinol (Lausanne). 2016 Dec 15;7:158. doi: 10.3389/fendo.2016.00158. eCollection 2016.
Preterm birth associates with a substantially increased risk of later cardiovascular disease and neurodevelopmental disorders. Understanding underlying mechanisms will facilitate the development of screening and intervention strategies to reduce disease risk. Changes in DNA methylation have been proposed as one mechanism linking the early environment with later disease risk. We tested the hypothesis that preterm birth associates with altered DNA methylation in genes encoding insulin-like growth factor 2 (IGF2) and FK506-binding protein 5 (FKBP5), which appear particularly vulnerable to early life adversity.
Fifty preterm infants were seen and assessed at birth, term equivalent age, 3 months and 1-year corrected ages; 40 term infants were seen at birth, 3 months and 1 year. Saliva was collected for DNA extraction at birth, term, and 1 year. Pyrosequencing of bisulfite-converted DNA was performed to measure DNA methylation at specific CpG sites within the and loci.
Weight and head circumference was reduced in preterm infants at all time points. Preterm infants had a higher percentage body fat at term-corrected age, but this difference was not persistent. DNA methylation at the differentially methylated region (DMR) of () and was lower in preterm infants at birth- and term-corrected age compared to term infants at birth. and methylation was related to birthweight SD score in preterm infants. Among preterm infants, social deprivation was an independent contributor toward reducing DNA methylation at at birth- and term-corrected age and maternal smoking was associated with reduced DNA methylation at at birth. There were no persistent differences in DNA methylation at 1 year of age.
Changes in DNA methylation were identified at key regions of and in preterm infants in early life. Potential contributing factors include maternal smoking and social deprivation. However, these changes did not persist at 1 year of age and further longitudinal studies are required to determine any associations between altered DNA methylation in the perinatal period of individuals born preterm and their long-term health.
早产与日后患心血管疾病和神经发育障碍的风险大幅增加相关。了解潜在机制将有助于制定筛查和干预策略以降低疾病风险。DNA甲基化的变化已被提出作为一种将早期环境与日后疾病风险联系起来的机制。我们检验了这样一个假设，即早产与胰岛素样生长因子2（IGF2）和FK506结合蛋白5（FKBP5）编码基因中的DNA甲基化改变有关，这两个基因似乎特别容易受到早期生活逆境的影响。
对50名早产儿在出生时、足月矫正年龄、3个月和1岁矫正年龄进行观察和评估；对40名足月儿在出生时、3个月和1岁进行观察。在出生时、足月时和1岁时收集唾液用于DNA提取。对亚硫酸氢盐转化后的DNA进行焦磷酸测序，以测量IGF2和FKBP5基因座内特定CpG位点的DNA甲基化。
早产儿在所有时间点的体重和头围均降低。早产儿在足月矫正年龄时体脂百分比更高，但这种差异并不持续。与出生时的足月儿相比，早产儿在出生时和足月矫正年龄时，IGF2和FKBP5的差异甲基化区域（DMR）的DNA甲基化较低。IGF2和FKBP5甲基化与早产儿的出生体重标准差评分相关。在早产儿中，社会剥夺是出生时和足月矫正年龄时降低IGF2 DNA甲基化的独立因素，而母亲吸烟与出生时FKBP5 DNA甲基化降低有关。1岁时DNA甲基化没有持续差异。
在生命早期，早产儿的IGF2和FKBP5关键区域存在DNA甲基化变化。潜在的影响因素包括母亲吸烟和社会剥夺。然而，这些变化在1岁时并未持续，需要进一步的纵向研究来确定早产个体围产期DNA甲基化改变与其长期健康之间的任何关联。
