Novel epigenetic link between gestational diabetes mellitus and macrosomia.

ABSTRACT

Background & objectives: Examine maternal gestational diabetes mellitus (GDM), macrosomia and DNA methylation in candidate genes IGF1, IGF2, H19, ARHGRF11, MEST, NR3C1, ADIPOQ and RETN. Materials & methods: A total of 1145 children (572 GDM cases and 573 controls) from the Tianjin GDM study, including 177 with macrosomia, had blood DNA collection at median age 5.9 (range 3.1-10.0). We used logistic regression to screen for associations with GDM and model macrosomia on 37 CpGs, and performed mediation analysis. Results: One CpG was associated with macrosomia at false discovery rate (FDR) <0.05 (cg14428359 in MEST); two (cg19466922 in MEST and cg26263166 in IGF2) were associated at p < 0.05 but mediated 26 and 13%, respectively. Conclusion:MEST and IGF2 were previously identified for potential involvement in fetal growth and development (Trial Registration number NCT01554358 [ClinicalTrials.gov]).

Lay abstract Many women who get gestational diabetes during pregnancy go on to give birth to larger (macrosomic) babies. These babies then grow up to have greater risk of being overweight or obese, and all the health concerns this entails. We sought to examine whether epigenetic factors could help explain this link, by examining the blood of some children whose mothers were enrolled in a gestational diabetes study in China. We identified three sites on two different genes as being associated with both gestational diabetes and macrosomia. The way these genes work suggest a mechanism for how they contribute to macrosomia, providing a promising new avenue for future research, early detection and precision prevention (Trial Registration number NCT01554358 [ClinicalTrials.gov]).