孕前体重指数对妊娠期糖尿病发病影响及关键基因的鉴定

Effect of Pre-pregnancy Body Mass Index on the Pregnancy Women with Gestational Diabetes Mellitus and Hub Gene Identification

基于加权基因共表达网络(weighted gene co-expression network analysis,WGCNA)分析妊娠期糖尿病胎盘组织mRNA与孕前体重指数(Pre-pregnancy body mass index,BMI)的相关性。寻找胎盘糖、脂代谢的关键基因,探索妊娠期糖尿病防治的新靶点。2018年5~7月纳入广西壮族自治区妇幼保健院新阳院区孕妇39例,妊娠期糖尿病组18例,健康对照组21例。收集孕妇病历资料、胎盘组织、脐血样本。通过胎盘组织mRNA测序,进行基因网络与临床指标相关性分析。妊娠期糖尿病组的孕前BMI、收缩压、舒张压、口服糖耐量实验(oral glucose tolerance test,OGTT)血糖浓度较对照组的显著增高(P<0.05)。多因素logistic回归分析孕前BMI(OR=1.336,95%CI=1.078~1.655,P=0.008)。WGCNA分析提示胎盘基因表达模块MEdarkorange与孕前BMI具有密切相关性(r=0.33,P=0.04),将该模块进行基因本体(gene ontology,GO)与KEGG(kyotoencyclopedia of genes and genomes,KEGG)通路分析,富集到糖、脂代谢以及氧化代谢相关关键通路,c-JUN、FOS、EGR1是该模块的关键基因。以上结果表明孕前高BMI是妊娠期糖尿病的独立危险因素,c-JUN、FOS、EGR1可能是妊娠期脂、糖代谢的关键基因。

Based on the weighted gene co-expression network analysis to analyze the correlation between placental tissue m RNA and pre-pregnancy body mass index in gestational diabetes.Our study focused on searching for the key genes in fat and glucose metabolism and exploring new targets for the prevention and treatment of gestational diabetes.From May to July 2018,39 pregnant women in Xinyang Hospital,Maternal and Child Health Hospital Care of Guangxi Zhuang Autonomous Region,18 cases in the gestational diabetes group,and 21 cases in the healthy control group were recruited.The subjects’medical records,placental tissue samples,and cord blood samples were collected.Placental tissue samples were used for transcriptome sequencing,and co-expression modules were constructed to correlate with clinical indicators.The gestational age index,pre-pregnancy BMI,systolic,and diastolic blood pressure,and blood glucose level in the oral glucose tolerance test of the gestational diabetes group were higher than those of the normal glucose tolerance group(P<0.05).Multi-variable logistic regression analysis indicated that pre-pregnancy BMI(odds ratio 95%confidence interval 1.336(1.078~1.655),P=0.008).A co-expression model of placenta tissue was constructed,and the key module(MEdarkorange)was correlated with prepregnancy BMI(r=0.33,P=0.04).The module was subjected to Gene Ontology and Ky oto Encyclopedia of Genes and Genomes pathway analysis,and enriched in fat,glucose metabolism and oxidative metabolism key pathway.The top of three hub genes,namely,c-JUN,FOS and EGR1,were finally confirmed.This research indicated that pre-pregnancy BMI is an independent risk factor of gestational diabetes mellitus,and c-JUN,FOS and EGR1 may be key genes in fat and glucose metabolism during pregnancy.