Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children

被引：91

作者：

Hjort, Line ^{[1
,2
,3
]}

Martino, David ^{[4
,5
]}

Grunnet, Louise Groth ^{[1
,3
]}

Naeem, Haroon ^{[6
,7
,8
]}

Maksimovic, Jovana ^{[5
,6
]}

Olsson, Anders Henrik ^{[1
]}

Zhang, Cuilin ^{[9
]}

Ling, Charlotte ^{[10
]}

Olsen, Sjurdur Frodi ^{[11
]}

Saffery, Richard ^{[5
,12
]}

Vaag, Allan Arthur ^{[1
,13
]}

机构：

[1] Rigshosp, Dept Endocrinol Diabet & Metab, Copenhagen, Denmark

[2] Univ Copenhagen, Fac Med & Hlth Sci, Copenhagen, Denmark

[3] Danish Diabet Acad, Odense, Denmark

[4] Murdoch Childrens Res Inst, Ctr Food & Allergy Res, Melbourne, Vic, Australia

[5] Univ Melbourne, Dept Pediat, Melbourne, Vic, Australia

[6] Murdoch Childrens Res Inst, Bioinformat Grp, Melbourne, Vic, Australia

[7] Monash Univ, Monash Bioinformat Platform, Clayton, Vic, Australia

[8] Univ Melbourne, Dept Comp & Informat Syst, Melbourne, Vic, Australia

[9] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD USA

[10] Lund Univ, Scania Univ Hosp, Diabet Ctr, Epigenet & Diabet Unit,Dept Clin Sci,CRC, Malmo, Sweden

[11] Statens Serum Inst, Ctr Fetal Programming, Copenhagen, Denmark

[12] Murdoch Childrens Res Inst, Canc & Dis Epigenet, Melbourne, Vic, Australia

[13] AstraZeneca, IMED Biotech Unit, Cardiovasc & Metab Dis CVMD Translat Med Unit, Early Clin Dev, Gothenburg, Sweden

来源：

JCI INSIGHT | 2018年 / 3卷 / 17期

关键词：

DNA METHYLATION; ADIPOSE-TISSUE; INTRAUTERINE EXPOSURE; GLUCOSE-TOLERANCE; CORD BLOOD; MELLITUS; GENES; WOMEN; EXPRESSION; PREGNANCY;

D O I：

10.1172/jci.insight.122572

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Offspring of women with gestational diabetes mellitus (GDM) are at increased risk of developing metabolic disease, potentially mediated by epigenetic mechanisms. We recruited 608 GDM and 626 control offspring from the Danish National Birth Cohort, aged between 9 and 16 years. DNA methylation profiles were measured in peripheral blood of 93 GDM offspring and 95 controls using the Illumina HumanMethylation450 BeadChip. Pyrosequencing was performed for validation/replication of putative GDM-associated, differentially methylated CpGs in additional 905 offspring (462 GDM, 444 control offspring). We identified 76 differentially methylated CpGs in GDM offspring compared with controls in the discovery cohort (FDR, P < 0.05). Adjusting for offspring BMI did not affect the association between methylation levels and GDM status for any of the 76 CpGs. Most of these epigenetic changes were due to confounding by maternal prepregnancy BMI; however, 13 methylation changes were independently associated with maternal GDM. Three prepregnancy BMI-associated CpGs (cg00992687 and cg09452568 of ESM1 and cg14328641 of MS4A3) were validated in the replication cohort, while cg09109411 (PDE6A) was found to be associated with GDM status. The identified methylation changes may reflect developmental programming of organ disease mechanisms and/or may serve as disease biomarkers.

引用

页数：14

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