缺氧诱导因子-3α甲基化与DNA损伤诱导转录物4在妊娠期糖尿病中的表达水平及其与妊娠结局的关系

doi:10.3969/j.issn.1006-5725.2024.24.010

Abstract

Abstract:

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.

Key words: gestational diabetes mellitus, HIF-3α, DDIT4, methylation, pregnancy outcome

CLC Number:

R714.256

Wenqing XU,Yishan LI,Qiuyu HAN,Fangjing SONG,Lin. MENG. Expression levels of HIF⁃3α methylation and DDIT4 in gestational diabetes mellitus and its relationship with pregnancy outcomes[J]. The Journal of Practical Medicine, 2024, 40(24): 3497-3502.

Figures/Tables 8

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References 22

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项目	对照组（n = 40）	GDM1组（n = 40）	GDM2组（n = 40）	F值	P值
年龄/岁	28.25 ± 3.53	28.45 ± 3.23	28.60 ± 2.36	0.130	0.878
分娩孕周/周	38.80 ± 1.04	38.27 ± 1.20	38.60 ± 1.08	2.282	0.107
孕前BMI/（kg/m²）	22.21 ± 0.92	24.23 ± 1.08	26.05 ± 1.27	121.340	< 0.001
FPG/（mmol/L）	4.70 ± 0.19	5.17 ± 0.29	5.92 ± 0.26	237.716	< 0.001
HbA_1c/%	4.89 ± 0.33	5.40 ± 0.20	6.40 ± 0.19	378.754	< 0.001
TC/（mmol/L）	4.15 ± 0.32	4.87 ± 0.38	5.18 ± 0.26	104.652	< 0.001
TG/（mmol/L）	1.57 ± 0.13	1.91 ± 0.19	2.57 ± 0.23	283.015	< 0.001
HDL-C/（mmol/L）	0.92 ± 0.17	0.91 ± 0.10	0.90 ± 0.12	0.344	0.710
LDL-C/（mmol/L）	2.14 ± 0.27	2.56 ± 0.25	2.95 ± 0.27	94.410	< 0.001
FINS/（mmol/L）	11.56 ± 0.28	12.05 ± 0.23	14.57 ± 0.19	1851.195	< 0.001
HOMA-β	198.82 ± 40.62	147.70 ± 21.62	121.81 ± 12.17	81.344	< 0.001
HOMA-IR	2.41 ± 0.13	2.77 ± 0.20	3.83 ± 0.21	641.397	< 0.001

项目	对照组（n = 40）	GDM1组（n = 40）	GDM2组（n = 40）	χ ² 值	P值
胎膜早破	2（5.00）	3（7.50）	18（45.00）^?#	16.705	< 0.001
羊水过多	3（7.50）	5（12.50）	15（37.50）^?#	11.318	0.003
早产儿	1（2.50）	2（5.00）	12（30.00）^?#	10.920	0.004
巨大儿	2（5.00）	4（10.00）	21（52.50）^?#	21.667	< 0.001
新生儿低血糖	2（5.00）	3（7.50）	17（42.50）^?#	15.745	< 0.001

项目	对照组（n = 40）	GDM1组（n = 40）	GDM2组（n = 40）
甲基化率	11（27.50）	14（35.00）	27（67.50）^?#
非甲基化率	29（72.50）	26（65.00）	13（32.50）^?#
χ² 值			14.729
P值			0.001

项目	HIF?3α		DDIT4
项目	r值	P值	r值	P值
胎膜早破	-0.224	0.014	-0.429	< 0.001
羊水过多	-0.262	0.004	-0.336	< 0.001
早产儿	-0.235	0.010	-0.384	< 0.001
巨大儿	-0.343	0.000	-0.518	< 0.001
新生儿低血糖	-0.253	0.005	-0.448	< 0.001

项目	妊娠结局良好组（n=43）	妊娠结局不良组（n=37）	t值	P值
年龄/岁	28.19 ± 3.18	28.79 ± 2.86	-1.048	0.297
分娩孕周/周	38.61 ± 1.22	38.48 ± 0.97	0.630	0.530
孕前BMI/（kg/m²）	23.86 ± 1.79	24.63 ± 2.03	-2.195	0.030
FPG/（mmol/L）	5.21 ± 0.54	5.35 ± 0.59	-1.385	0.169
HbA_1c/%	5.47 ± 0.67	5.71 ± 0.67	-1.861	0.065
TC/（mmol/L）	4.68 ± 0.58	4.81 ± 0.46	-1.422	0.158
TG/（mmol/L）	1.95 ± 0.45	2.12 ± 0.44	-2.058	0.042
HDL-C/（mmol/L）	0.90 ± 0.12	0.92 ± 0.16	-0.554	0.581
LDL-C/（mmol/L）	2.53 ± 0.45	2.59 ± 0.38	-0.734	0.464
FINS/（mmol/L）	12.50 ± 1.25	13.06 ± 1.42	-2.235	0.028
HOMA-β	156.47 ± 34.09	155.57 ± 52.32	0.115	0.909
HOMA-IR	2.92 ± 0.60	3.14 ± 0.67	-1.863	0.066
HIF?3α mRNA	0.98 ± 0.21	0.83 ± 0.19	4.222	< 0.001
DDIT4 mRNA	1.18 ± 0.26	0.87 ± 0.29	6.067	< 0.001

Expression levels of HIF⁃3α methylation and DDIT4 in gestational diabetes mellitus and its relationship with pregnancy outcomes

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变量	B	SE	Wald χ²	P值	OR	95% CI
孕前BMI	0.075	0.181	0.170	0.680	1.078	0.755 ~ 1.537
TG	-0.950	1.129	0.709	0.400	0.387	0.042 ~ 3.532
FINS	0.031	0.362	0.007	0.932	1.031	0.508 ~ 2.095
HIF?3α mRNA	-3.352	1.232	7.403	0.007	0.035	0.003 ~ 0.392
DDIT4 mRNA	-4.036	0.965	17.482	< 0.001	0.018	0.003 ~ 0.117

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