Epigenetic modification of the pentose phosphate pathway and the IGF-axis in women with gestational diabetes mellitus

被引：20

作者：

Steyn, Angela ^{[1
,2
]}

Crowther, Nigel J. ^{[1
,2
,3
]}

Norris, Shane A. ^{[4
]}

Rabionet, Raquel ^{[5
]}

Estivill, Xavier ^{[5
]}

Ramsay, Michele ^{[1
,2
,6
]}

机构：

[1] Univ Witwatersrand, Fac Hlth Sci, Natl Hlth Lab Serv, Div Human Genet, Johannesburg, Gauteng, South Africa

[2] Univ Witwatersrand, Sch Pathol, Fac Hlth Sci, Johannesburg, Gauteng, South Africa

[3] Univ Witwatersrand, Sch Pathol, Dept Chem Pathol, Johannesburg, Gauteng, South Africa

[4] Univ Witwatersrand, Dev Pathways Hlth Res Unit, Johannesburg, Gauteng, South Africa

[5] Ctr Genom Regulat, Genes & Dis Program, Barcelona, Spain

[6] Univ Witwatersrand, Fac Hlth Sci, Sydney Brenner Inst Mol Biosci, Johannesburg, Gauteng, South Africa

来源：

EPIGENOMICS | 2019年 / 11卷 / 12期

基金：

英国医学研究理事会;

关键词：

DNA methylation; epigenetics; gestational diabetes mellitus; glucose-6-phosphate dehydrogenase; IGF binding protein; pentose phosphate pathway; RNA sequencing; GLUCOSE INHIBITS GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; OXIDATIVE STRESS; GENE-EXPRESSION; PREGNANT-WOMEN; INSULIN; BINDING; HYPERGLYCEMIA; EPIDEMIOLOGY; DISEASE; TOPHAT;

D O I：

10.2217/epi-2018-0206

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Aim: Gestational diabetes mellitus (GDM) has been linked with adverse long-term health outcomes for the fetus and mother. These effects may be mediated by epigenetic modifications. Materials & methods: Genome-wide RNA sequencing was performed in placental tissue and maternal blood in six GDM and six non-GDM pregnancies. Promoter region DNA methylation was examined for selected genes and correlated with gene expression to examine an epigenetic modulator mechanism. Results: Reductions of mRNA expression and increases in promoter methylation were observed for G6PD in GDM women, and for genes encoding IGF-binding proteins in GDM-exposed placenta. Conclusion: GDM involves epigenetic attenuation of G6PD, which may lead to hyperglycemia and oxidative stress, and the IGF-axis, which may modulate fetal macrosomia.

引用

页码：1371 / 1385

页数：15

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