PDX1基因甲基化、NGN3及Pax6基因水平与妊娠期糖尿病及妊娠结局关系的研究

The relationship between PDX1 gene methylation,NGN3 and Pax6 gene expressions and gestational diabetes mellitus and pregnancy outcome

目的探讨胰腺和十二指肠同源框1(PDX1)基因甲基化、NGN3 mRNA、Pax6 mRNA水平与GDM及妊娠结局的关系。方法选取妊娠24~28周孕妇246例,根据75 g OGTT检查结果分为GDM组和糖耐量正常组(NGT组),采用甲基化特异PCR法检测PDX1甲基化率,RT-PCR检测PDX1基因表达,分析PDX1甲基化及基因水平与GDM及其妊娠结局的关系。结果GDM组FPG、FC-P、TC、TG、LDL-C、FIns、HOMA-IR、剖宫产率、巨大儿及早产儿发生率高于NGT组(P<0.05),PDX1基因非甲基化率、PDX1 mRNA、NGN3 mRNA及Pax6 mRNA相对表达量均低于NGT组(P<0.05)。GDM患者PDX1基因甲基化组FPG、FC-P、TG、TC、LDL-C、FIns、HOMA-IR高于非甲基化组(P<0.01),PDX1、NGN3、Pax6低于非甲基化组(P<0.01)。PDX1、NGN3及Pax6 mRNA对GDM诊断有较高的灵敏度、特异度。妊娠次数、孕前BMI、TG、HOMA-IR及PDX甲基化率是GDM发生的危险因素,PDX1mRNA、NGN3 mRNA是GDM发生的保护因素。结论PDX1基因甲基化及PDX1、NGN3、Pax6基因表达降低与GDM发生相关,其作用机制尚需进一步明确,未发现PDX1基因甲基化率与GDM不良妊娠结局相关。

Objective To investigate the relationship between the level of pancreatic and duodenal homeobox 1(PDX1)gene methylation,the expressions of NGN3 mRNA and Pax6 mRNA and gestational diabetes mellitus(GDM)as well as pregnancy outcome.Methods A total of 246 women with 24~28 gestational weeks were enrolled.According to the results of 75 g OGTT,these pregnant women were divided into GDM group and normal glucose tolerance group(NGT group).Methylation-specific PCR was used to detect the rate of PDX1 methylation.The expression of PDX1 gene was detected by RT-PCR.Results Compared with NGT group,the levels of FPG,FC-P,TC,TG,LDL-C,FIns and HOMA-IR and the incidences of cesarean section,giant infants and premature infants were higher in GDM group(P<0.05),while the rate of PDX1 gene unmethylated and the relative expressions of PDX1,NGN3 and Pax6 mRNA were lower(P<0.05).Compared with PDX1 unmethylated group in pregnant women,the levels of FPG,FC-P,TG,TC,LDL-C,FIns and HOMA-IR in PDX1 gene methylation group were higher(P<0.01),while the expressions PDX1,NGN3 and Pax6 were lower(P<0.01).PDX1,NGN3 and Pax6 mRNA have high sensitivity and specificity for GDM diagnosis.The number of pregnancies,pre-pregnancy BMI,TG,HOMA-IR and PDX methylation rate were the risk factors for GDM.PDX1 mRNA and NGN3 mRNA were the protective factors for GDM.Conclusion PDX1 gene methylation and the decreased expressions of PDX1,NGN3 and Pax6 genes were associated with the occurrence of GDM.No correlation was found between the PDX1 gene methylation rate and the adverse outcome of GDM.