妊娠期糖尿病患者基因DNA甲基化的研究进展

doi:10.3969/j.issn.1674-8115.2021.08.021

摘要/Abstract

摘要：

妊娠期糖尿病是指患者妊娠前糖代谢正常、妊娠期出现的糖耐量异常，表现为机体脂肪、肌肉等组织对胰岛素的敏感性降低，血糖水平异常，严重影响母体及子代健康。妊娠期糖尿病患者在产后及其子代罹患2型糖尿病及其他代谢性疾病的风险明显增加。研究发现，表观遗传修饰如DNA甲基化参与妊娠期糖尿病的发生及母胎并发症的发生过程。在妊娠期糖尿病患者多种临床标本如胎盘、脐血、外周血与脂肪等组织中，发现多个基因的甲基化水平改变，并可通过“胎儿编程”的方式影响子代终生。该文对妊娠期糖尿病相关基因的DNA甲基化研究进展进行综述。

关键词: 妊娠期糖尿病, 表观遗传修饰, DNA甲基化, 胎儿编程, 代谢模式

Abstract:

Gestational diabetes mellitus refers to patients with normal glucose metabolism before pregnancy and getting abnormal glucose tolerance during pregnancy. It is characterized by decreased insulin sensitivity of adipose and muscle tissues and abnormal blood glucose levels in the body. This disease can seriously affect the maternal and fetal health, and the risk of type 2 diabetes mellitus and other metabolic diseases in the postpartum period and the offsprings significantly increased. It has been found that epigenetic modifications such as DNA methylation can be involved in the pathogenesis of gestational diabetes mellitus and the occurrence of maternal and fetal complications. The differences in gene methylation levels appear in the various clinical specimens of patients with gestational diabetes mellitus, such as placentas, umbilical cord blood, peripheral blood and adipose tissues. It can also affect all the lives of the offsprings through “fetal programming”. In this paper, the research progress of DNA methylation in gestational diabetes mellitus is reviewed.

Key words: gestational diabetes mellitus (GDM), epigenetic modification, DNA methylation, fetal programming, metabolic pattern

中图分类号:

R714.256

吴丹, 葛莉萍. 妊娠期糖尿病患者基因DNA甲基化的研究进展[J]. 上海交通大学学报(医学版), 2021, 41(8): 1120-1124.

Dan WU, Li-ping GE. Research progress of DNA methylation in gestational diabetes mellitus[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(8): 1120-1124.

图/表 1

参考文献 47

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Specimen type	Gene involved in methylation	Impact of changes in methylation levels	Reference
Maternal side of placenta （from the mother， Homo sapiens）	DLK1	Glycemia	［6］
	PPARGC1， PDX1	Fetal glucose metabolism	［7］
	IGF2	Birth weight	［8］
	PPARGC1A	Newborn birth weight	［9-10］
	LPL	Energy homeostasis	［11］
	MEST， NR3C1	Obesity	［13］
	G6PD， IGF	Hyperglycemia， oxidative stress and fetal macrosomia	［14］
Peripheral blood （from the mother， Homo sapiens）	CAMTA1	Insulin synthesis and secretion	［26］
	IL10	Inflammation	［28］
	G6PD， IGF	Hyperglycemia， oxidative stress and fetal macrosomia	［14］
	NDUFC1， HAPLN3， RHOG， et al	Cell morphology， cellular organization and cell cycle	［27］
Cord blood （from the mother， Homo sapiens）	OR2L13， CYP2E1	Autism and diabetes	［21］
	IGF2	Fetal growth and newborn birth weight	［8］
	MEST， NR3C1	Obesity predisposition	［13］
	HIF3A， et al	Metabolic phenotype	［20］
	ARHGEF11	Macrosomia	［18］
Adipose and omental tissue （from the mother， Homo sapiens）	TNF， SOCS3	Inflamation	［29］
	HIF3A	Insulin resistance	［30］
	MSLN	Antigen process and presentation	［33］
Umbilical cord blood lymphocyte （from the mother， Homo sapiens）	MCAT	Mitochondrial fatty acid synthesis and insulin resistance	［23］
Fetal side of the placenta （from the offspring， Homo sapiens）	DLK1	Newborn birth weight	［6］
	LPL	Energy homeostasis	［12］
Adipose tissue （from the offspring， Homo sapiens）	PPARGC1A	Insulin secretion and metabolic disease	［40］
	ADIPOQ， RETN	Metabolic disease	［34］
Muscle （from the offspring， Homo sapiens）	PPARGC1A	Insulin secretion and metabolic disease	［40］
Dental epithelial stem cell （from the offspring， Homo sapiens）	APEX1	Proliferation and self-renew	［41］
Pancreas （from the offspring， Mus musculus）	Gnas， Fbp2， Wnt2， et al	Glycolipids metabolism	［35］
Pancreatic islet （from the offspring， Mus musculus）	Abcc8， et al	Insulin secretion	［36］
Heart （from the offspring， Mus musculus）	Sirt1	Heart ischemia sensitive phenotype	［45］
Placenta （from the offspring， Mus musculus）	Dlk1， et al	Insulin pathway	［39］
Primordial germ cell （from the offspring， Mus musculus）	Fyn	Obesity and insulin resistance	［37］

Specimen type	Gene involved in methylation	Impact of changes in methylation levels	Reference
Maternal side of placenta （from the mother， Homo sapiens）	DLK1	Glycemia	［6］
	PPARGC1， PDX1	Fetal glucose metabolism	［7］
	IGF2	Birth weight	［8］
	PPARGC1A	Newborn birth weight	［9-10］
	LPL	Energy homeostasis	［11］
	MEST， NR3C1	Obesity	［13］
	G6PD， IGF	Hyperglycemia， oxidative stress and fetal macrosomia	［14］
Peripheral blood （from the mother， Homo sapiens）	CAMTA1	Insulin synthesis and secretion	［26］
	IL10	Inflammation	［28］
	G6PD， IGF	Hyperglycemia， oxidative stress and fetal macrosomia	［14］
	NDUFC1， HAPLN3， RHOG， et al	Cell morphology， cellular organization and cell cycle	［27］
Cord blood （from the mother， Homo sapiens）	OR2L13， CYP2E1	Autism and diabetes	［21］
	IGF2	Fetal growth and newborn birth weight	［8］
	MEST， NR3C1	Obesity predisposition	［13］
	HIF3A， et al	Metabolic phenotype	［20］
	ARHGEF11	Macrosomia	［18］
Adipose and omental tissue （from the mother， Homo sapiens）	TNF， SOCS3	Inflamation	［29］
	HIF3A	Insulin resistance	［30］
	MSLN	Antigen process and presentation	［33］
Umbilical cord blood lymphocyte （from the mother， Homo sapiens）	MCAT	Mitochondrial fatty acid synthesis and insulin resistance	［23］
Fetal side of the placenta （from the offspring， Homo sapiens）	DLK1	Newborn birth weight	［6］
	LPL	Energy homeostasis	［12］
Adipose tissue （from the offspring， Homo sapiens）	PPARGC1A	Insulin secretion and metabolic disease	［40］
	ADIPOQ， RETN	Metabolic disease	［34］
Muscle （from the offspring， Homo sapiens）	PPARGC1A	Insulin secretion and metabolic disease	［40］
Dental epithelial stem cell （from the offspring， Homo sapiens）	APEX1	Proliferation and self-renew	［41］
Pancreas （from the offspring， Mus musculus）	Gnas， Fbp2， Wnt2， et al	Glycolipids metabolism	［35］
Pancreatic islet （from the offspring， Mus musculus）	Abcc8， et al	Insulin secretion	［36］
Heart （from the offspring， Mus musculus）	Sirt1	Heart ischemia sensitive phenotype	［45］
Placenta （from the offspring， Mus musculus）	Dlk1， et al	Insulin pathway	［39］
Primordial germ cell （from the offspring， Mus musculus）	Fyn	Obesity and insulin resistance	［37］

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