超重孕妇低生糖负荷膳食干预对新生儿DNA甲基化影响的探索性研究

目的通过对超重孕妇实施低血糖生成指数(GI)膳食的干预，探讨胎盘组织和脐血中与体重增长有关基因的甲基化的改变。 方法采用随机化单盲对照干预试验设计，研究对象为初次产检孕周≤12周且体重超重的孕妇。以研究对象纳入的顺序号为随机序列号，采用简单随机化的方法随机分为干预组和对照组。干预组在中国孕妇保健规范的基础上结合国家对孕妇的膳食和体力活动规范实施低GI膳食指导干预 ，对照组仅按照国家规范给予指导，不给予低GI膳食的指导。两组分别在孕早期、中期和晚期干预3次。 干预组和对照组各纳入25例。孕妇分娩时收集胎盘组织和脐血，提取DNA，采用Illumina甲基化芯片进行两步法全基因组甲基化测定。 结果孕妇孕期相关暴露因素在干预组与对照组差异无统计学意义；胎儿出生体重干预组高于对照组［（3.7±0.5） vs (3.5±0.4) kg］，但差异无统计学意义(P=0.248)。本研究结果结合生物信息数据库分析，筛选出19个基因位点，所属18个基因，其中5个基因位于1号染色体，2个基因位于7号染色体，其余基因分布分散。比较干预组与对照组甲基化的改变，发现脐血中2个差异的甲基化CpG位点，分别位于TEKT5和MIR378C基因上,胎盘组织中1个差异的甲基化CpG位点，所属PGBD5基因。 结论通过对超重孕妇采取低GI膳食干预，胎盘组织和脐血中基因的甲基化可以发生改变，为中国超重、肥胖孕妇疾病的预防提供新的方法，对子代的健康成长有重要的意义。

Exploratory study on the diet intervention during pregnancy to overweight pregnant women--effect of low glycemic load diet on DNA methylation of placenta tissue and cord blood of neonates

ObjectiveTo evaluate whether the low glycemic load diet intervention during pregnancy to overweight pregnant women have any impact on DNA methylation in placenta tissue and cord blood of their neonates. MethodsRandomized, single blinded, controlled intervention trial was selected. Overweight pregnant women (BMI≥24 kg·m-2) were recruited at first prenatal visit within 12 gestational weeks. Subjects were randomized by simple randomization and allocated into two groups, intervention group and control group. The intervention group was provided 3 times diet consultation about low glycemic load diet combined with the national diet and physical activity recommendations for pregnant women. The control group was given only national diet and physical acitivity recommendations. This paper included the first recruited 50 overweight pregnant women. Placenta tissue and cord blood sample were collected at delivery and properly treated according to standard protocol. The methylation of the placenta tissue DNA and umbilical cord blood DNA was detected by two-step genome wide methylation-based association analysis strategy. Illumina 450K whole genome Beadchip was applied for the first stage differential methylation analysis, and Illumina custom designed Goldengate methylation chip was used for the second stage methylation association analysis. ResultsBirth weight of intervention group was heavier than control group, (3.7±0.5) vs (3.5±0.4) kg, but the difference was not significant(P=0.248). The meathylation of 2 of 19 CpG sites was significantly different in umbilical cord blood between two groups, locating in TEKT5 and MIR378 gene, respectively. However, there was 1 of 19 CpG sites significantly different in placenta tissue which located in PGBD5. ConclusionThese novel data provided evidence that neonatal DNA methylation varied with low glycemic index diet intervention during pregnancy to overweight pregnant women. The long-term stablity and potential contribution of these changes to clinical postnatal outcomes need further investigation.