摘要
目的探讨胎盘胰岛索样生长因子1（insulinlikegrowthfactor1，IGF-1）基因表达和甲基化变化与巨大儿发生的关系。方法选择2011年4月至2012年3月在温州医科大学附属育英儿童医院正常妊娠并足月分娩的129名产妇和新生儿为研究对象，其中59例为巨大儿、70名为正常体重儿。调查产妇和新生儿的基本信息。并收集胎盘样品。实时荧光定量PCR检测胎盘IGF-1 mRNA的表达量，MassARRAY系统测定胎盘IGF-1基因启动子区CpG位点的甲基化水平。结果与正常体重儿比较，巨大儿胎盘IGF-1表达量和胎盘IGF-1甲基化水平的差异无统计学意义（P值分别为0．967、0．925）。胎盘mRNA表达量和IGF-1甲基化水平亦无统计学意义的相关性（r=0．128，P=0．295）。巨大儿与正常体重儿胎盘启动子区的CpG位点均呈低甲基化状态。以所有出生体重的上四分位数间距（4260g）为拐点，出生体重〈4260g组的mRNA表达量显著高于≥4260g组（r=2．806，P=0．005），且与出生体重呈正相关关系（r=0．264，P=0．022）。表明在出生体重〈4260g范围内，IGF-1表达量的增加贡献于出生体重的增长。但当胎儿过大时，存在负反馈调节作用，使表达量降低，以限制胎儿过度增大。结论胎盘IGF-1的表达量与出生体重呈双向性关联，其表达量的高低均与处于低甲基化状态的胎盘IGF-1的甲基化程度无关。
Objective To explore the correlation between methylation of insulin like growth factor 1 （IGF-1）gene promoter and its placenta-specific expression and fetal macrosoma. Methods One hundred twenty nine healthy pregnant women were recruited between April 2011 and March 2012. Baseline data were collected with self-report questionnaires. Real-time quantitative PCR was used to determine the expression of IGF-1 mRNA in the placenta. Methylation level of the IGF-1 gene was determined with matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Results The expression of IGF-1 in placenta and its methylation level showed no significant difference between macrosomic fetuses and controls. No linear correlation was found between IGF-1 mRNA expression and methylation level of IGF-1 promoter （r= 0. 128, P=0. 295）. IGF-1 promoter region in placenta showed a hypomethylalion status. However, a positive correlation was found between IGF-1 expression and birth weight below 4260 g （r=0. 264, P=0. 022）. The expression of IGF-1 mRNA was significantly higher in those with a birth weight below 4260 g, which suggested that placental IGF-1 expression may contribute to increased birth weight. In regard to fetal overgrowth, however, there seemed to be a negative correlation in which placental IGF-1 expression was downregulated to limit fetal overgrowth. Conclusion No linear correlation was found between placental IGF-1 expression and methylation level of IGF-1 promoter with a hypomethylation status. The contribution of placental IGF-1 expression to birth weight is bidirectional. Increased expression seems to promote fetalgrowth, while decreased expressions may curb overgrowth, therefore control fetal growth in a relativelynormal range.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2015年第1期36-39,共4页
Chinese Journal of Medical Genetics
基金
国家自然科学基金（81072378）
浙江省自然科学基金（Y2101185）
