目的 探讨妊娠期糖尿病（GDM）孕妇外周血中HIF?3α基因甲基化、HIF?3α mRNA、DDIT4 mRNA的表达水平及其与妊娠结局的关系，为GDM孕妇的妊娠监督及临床诊治提供思路，以降低不良妊娠结局的风险。 方法 随机选取2023年3月至2024年3月于徐州医科大学附属医院住院分娩的GDM孕妇80例，分为血糖控制良好组（GDM1组，40例）和血糖控制不良组（GDM2组，40例），另选取同期无妊娠合并症或并发症孕妇40例为对照组。采用甲基化特异PCR法检测HIF?3α甲基化率，实时荧光定量PCR法检测HIF?3α mRNA、DDIT4 mRNA水平。对比分析3组数据，统计不良妊娠结局，分析HIF?3α mRNA、DDIT4 mRNA与各项不良妊娠结局的相关性，并进行不良妊娠结局logistic回归分析。 结果 GDM1组及GDM2组孕前BMI、FPG、HbA_1c、TC、TG、LDL-C、FINS、HOMA-IR均高于对照组（P < 0.05），HOMA-β低于对照组（P < 0.05）。GDM1组及GDM2组各项不良妊娠结局发生率均高于对照组，且GDM2组与对照组差异有统计学意义（P < 0.05），而GDM1组与对照组差异无统计学意义（P > 0.05）。与对照组相比，GDM1组及GDM2组HIF?3α基因甲基化率更高，HIF-α、DDIT4 mRNA表达水平更低，且GDM2组与对照组差异有统计学意义（P < 0.05），GDM1组与对照组差异无统计学意义（P > 0.05）。GDM孕妇各项不良妊娠结局与HIF?3α及DDIT4 mRNA表达水平均呈负相关（r < 0，P < 0.05）。HIF?3α mRNA和DDIT4 mRNA是不良妊娠结局发生的保护因素（OR < 1，P < 0.05）。 结论 HIF?3α甲基化率升高、HIF?3α及DDIT4基因表达降低与GDM发生发展有关，可能是导致不良妊娠结局的重要因素。

Objective To investigate the methylation levels of the HIF?3α gene， as well as the expression of HIF?3α mRNA and DDIT4 mRNA in peripheral blood samples from pregnant women with gestational diabetes mellitus （GDM）， and their association with pregnancy outcomes， aiming to provide insights for pregnancy monitoring and clinical diagnosis and treatment of GDM patients， thereby mitigating the risk of adverse pregnancy outcomes. Methods From March 2023 to March 2024， a total of 80 pregnant women with GDM were randomly selected at the Affiliated Hospital of Xuzhou Medical University. They were divided into two groups based on glycemic control： GDM1 （n = 40） representing good glycemic control and GDM2 （n = 40） representing poor glycemic control. Additionally， a control group consisting of 40 pregnant women without any pregnancy complications or comorbidities was included. Methylation-specific PCR was employed to determine the rate of HIF-3α methylation， while quantitative real-time PCR was used to assess the expressions of HIF-3α mRNA and DDIT4 mRNA. Adverse pregnancy outcomes were recorded across all three groups， and correlations between HIF-3α mRNA， DDIT4 mRNA， and various adverse pregnancy outcomes were analyzed using logistic regression analysis. Results Prior to pregnancy， GDM1 and GDM2 groups exhibited higher levels of FPG， HbA_1c， TC， TG， LDL-C， FINS and HOMA-IR （P < 0.05）， as well as lower levels of HOMA-β compared to the control group （P < 0.05）. The incidence of adverse pregnancy outcomes was also higher in both GDM groups than in the control group； this difference was significant for GDM2 （P < 0.05） but not for GDM1 （P > 0.05）. Furthermore， methylation rates of the HIF-3α gene were higher in both GDM groups compared to controls while expression levels of HIF-3α and DDIT4 mRNA were lower； these differences were significant for the GDM2 group versus controls （P < 0.05） but not for the GDM1 group versus controls （P > 0.05）. Finally， all adverse pregnancy outcomes among women with gestational diabetes mellitus showed a negative correlation with expression levels of both HIF-3α and DDIT4 mRNA （r < 0，P < 0.05）； moreover， these two mRNAs served as protective factors against such outcomes occurring（OR < 1，P < 0.05）. Conclusion The higher methylation rate of HIF-3α and the decreased expression of HIF-3α and DDIT4 genes are associated with the development of GDM and may serve as significant factors contributing to adverse pregnancy outcomes.