小于胎龄儿与IGF-2信号通路的遗传流行病学研究

Small for gestational age (SGA) is defined as infants with a birth weight below the 10th percentile for gestational age. Since it is closely related to maternal and neonatal complications during the perinatal period, short stature during the process of children's growth, especially to diabetes after adulthood, it is extremely important to explore the pathogenesis of SGA. Studies have shown that genetic factors combined with environmental factors are the important causes leading to SGA. The latest hypothesis of SGA genetic susceptibility is the dysfunction of IGF signal pathway; however, studies on the relationship between the associated gene SNPs of IGF-2/PI3K/Akt/mTOR signal pathway, gene-environmental interaction and SGA have not yet to be seen currently. Under the principle of informed consent, a case-control study was conducted, which included 1000 SGA infants and 1000 normal controls. Methods employed collecting cord blood samples, questionnaire to review the related risk factors, detecting the SNPs using whole genomic sequencing and SNaPshot method, and understanding the relationship between SGA and methylation status of IGF-2/H19. Furthermore, the multiple factor dimension reduction method (GMDR) and Logistic regression were selected to test the relationship between gene-gene interaction, gene-environmental interaction and SGA to explore the influences of genetic susceptibility factors and environmental factors on SGA. Ultimately we expect to clarify the pathogenesis of SGA, and to provide the theoretical basis for prevention and early diagnosis and treatment of SGA.

小于胎龄儿(SGA)是指出生体重低于同胎龄第10百分位数的新生儿，因其与母婴并发症、儿童矮小症及成年糖尿病等密切相关，所以探究SGA发病机制十分重要。研究表明，遗传因素与环境因素共同作用是SGA发病的主要原因。其中IGF信号通路功能紊乱是SGA遗传易感性的最新假说，但目前涉及IGF-2/IGF-1R/PI3K/Akt/mTOR信号通路的基因SNP位点及基因-环境交互作用与SGA的关系尚未见到。本研究拟采用病例对照研究，收集SGA患者和对照各1000名为研究对象，采集脐血并调查相关危险因素；应用全基因组测序和SNaPshot方法筛查检测基因SNP位点，并了解印迹基因IGF-2/H19甲基化与SGA的关系；通过多因子降维法、logistic回归等方法分析基因-基因、基因-环境之间交互作用与SGA的关系，探索遗传因素和环境因素对SGA的影响，阐明SGA发病机制，为SGA的预防及早期诊治提供依据。

小于胎龄儿(SGA)是指出生体重低于同胎龄第10百分位数的新生儿，因其与母婴并发症、儿童矮小症及成年糖尿病等密切相关，所以探究SGA发病机制十分重要。课题组首先通过在中国30个省份进行的回顾性队列研究，确定了中国30个省份低出生体重儿（low birth weight，LBW）的危险因素以及LBW发病率的地域差异，同时构建了河北省新生儿胎龄体重参考标准。此外，课题组利用机器学习模型，通过卫星数据估算妊娠期PM2.5浓度，发现了孕期PM2.5暴露和出生体重间的关联。课题组还发现，SGA患儿在2岁时伴随追赶性生长出现的肥胖与出生3月时的身高有关，可作为SGA出现超重/肥胖的早期预测指标。此外，课题组申请注册Clinical trial《Multicentral Hospital Cohort Study of Small for Gestational Age on Growth and Development》(ChiCTR1800016060)。该研究将首次系统观察我国儿童生长发育状况，并首次完整探讨遗传、环境和其他诸因素对生长发育的影响，为国内SGA相关研究及预警机制提供理论基础，最终实现SGA的早期干预。