摘要目的 研究胰岛素样生长因子2(IGF2)/HI9基因在妊娠期糖尿病(GDM)母亲分娩的足月小于胎龄儿外周血中启动子甲基化状态和mRNA表达情况及其临床意义.方法 收集2015年1月至2018年1月长沙市妇幼保健院妇产科GDM母亲分娩的20例足月小于胎龄儿(组1)及同期孕期身体健康母亲分娩的23例足月小于胎龄儿(组2)和21例健康足月新生儿(组3)的临床资料.应用亚硫酸氢盐测序法(BSP)对3组新生儿外周血中DNA IGF2/H19基因的甲基化进行检测,同时利用实时定量聚合酶链反应(RT-PCR)方法对IGF2 mRNA/H19进行检测.结果 组1新生儿外周血IGF2、H19启动子甲基化频率为(22.51±5.29)％和(28.94±2.51)％,组2 IGF2、H19启动子甲基化频率为(27.84±4.63)％和(34.58±6.97)％,组3 IGF2、H19启动子甲基化频率为(37.47±7.84)％和(40.26±5.33)％;组1的IGF2、H19启动子甲基化频率明显低于组2和组3,差异均有统计学意义(均P＜0.05).组1外周血中IGF2及H19 mRNA表达水平(1.46±0.21、1.39±0.17)明显高于组3(1.04±0.12、1.01±0.13),差异均有统计学意义(均P＜0.05).组1血中IGF2及H19mRNA表达水平与组2(1.30±0.10、1.29±0.11)比较,差异均无统计学意义(均P＞0.05).结论 小于胎龄儿暴露于孕期高血糖环境中会发生IGF2/H19基因甲基化频率和mRNA异常,这可能是其宫内发育迟缓原因之一,并可能影响其以后的生长发育.

abstractsObjective To investigate the promoter methylation status,mRNA expression and clinical significance of insulin-like growth factors 2 (IGF2)/H19 genes in term infants smaller than gestational age (SGA) infants whose mothers had gestational diabetes mellitus (GDM).Methods The clinical data of 20 full-term infants whose mothers had GDM (group 1),23 cases of full-term SGA infants whose mothers did not have GDM (group 2) and 21 full-term health infants whose mothers did not have any diseases during pregnancy(group 3) were collected,and all infants were delivered in Changsha Hospital for Maternal and Child Health Care between January 2015 and January 2018.The promoter methylation levels of IGF2/H19 gene from peripheral blood of 3 groups were detected by the method of Bisulfite sequencing polymerase chain reaction (PCR) (BSP),and IGF2/H19 mRNA was detected by real-time transcription RT-PCR method.Results The promoter methylation rates of IGF2/H19 in peripheral blood of infants were (22.51 ±5.29)％,(28.94 ±2.51)％ in group 1,(27.84 ±4.63)％,(34.58 ±6.97)％ in group 2,(37.47 ±7.84) ％,and (40.26 ±5.33) ％ in group 3.The promoter methylation rate of IGF2 and H19 in group 1 were significantly lower than those in group 2 and group 3,and the differences were statistically significant(all P ＜ 0.05).The relative expression of IGF2/H19 mRNA in peripheral blood of group 3 (1.04 ±0.12,1.01 ±0.13) were significantly higher than those in the group 1,and the differences were statistically significant (all P ＜ 0.05),and there were no significant differences in relative expression of IGF2/H19 between the group 1 and the group 2 (1.30 ±0.10,1.29 ±0.11) (all P ＞ 0.05).Conclusions The abnormal promoter methylation status and mRNA expression levels of IGF2/H19 gene methylation frequency and mRNA abnormalities may occur in infants less than gestational age infants if exposed to hyperglycemia during pregnancy,which may be one of the causes of intrauterine growth retardation and may affect its later growth and development.