1. Dichotomy in the Impact of Elevated Maternal Glucose Levels on Neonatal Epigenome
- Author
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Ai Ling Teh, Yap Seng Chong, Jerry Kok Yen Chan, Keith M. Godfrey, Xinyi Lin, Li Chen, Johan G. Eriksson, Neerja Karnani, Ives Lim, Yung Seng Lee, Mary Foong-Fong Chong, Julia L. MacIsaac, Yonghui Wu, Menglan He, Shiao-Yng Chan, Michael J. Meaney, Kok Hian Tan, Michael S. Kobor, Peter D. Gluckman, Clinicum, Johan Eriksson / Principal Investigator, and Department of General Practice and Primary Health Care
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,GENES ,Offspring ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Context (language use) ,INSULIN-SECRETION ,Biochemistry ,Body Mass Index ,Epigenesis, Genetic ,Epigenome ,Endocrinology ,2h oral glucose tolerance test ,Pregnancy ,Internal medicine ,IMPAIRED FASTING GLUCOSE ,medicine ,fasting plasma glucose ,Humans ,TOLERANCE ,Glycemic ,PLASMA-GLUCOSE ,business.industry ,Biochemistry (medical) ,Infant, Newborn ,GESTATIONAL DIABETES-MELLITUS ,Fasting ,DNA Methylation ,medicine.disease ,PREVALENCE ,Gestational diabetes ,Diabetes, Gestational ,Glycemic index ,3121 General medicine, internal medicine and other clinical medicine ,Prenatal Exposure Delayed Effects ,Cohort ,RISK-FACTORS ,CpG Islands ,Female ,gestational diabetes ,epigenome wide association study ,business ,Maternal Age - Abstract
Context Antenatal hyperglycemia is associated with increased risk of future adverse health outcomes in both mother and child. Variations in offspring’s epigenome can reflect the impact and response to in utero glycemic exposure, and may have different consequences for the child. Objective We examined possible differences in associations of basal glucose status and glucose handling during pregnancy with both clinical covariates and offspring cord tissue DNA methylation. Research Design and Methods This study included 830 mother-offspring dyads from the Growing Up in Singapore Towards Healthy Outcomes cohort. The fetal epigenome of umbilical cord tissue was profiled using Illumina HumanMethylation450 arrays. Associations of maternal mid-pregnancy fasting (fasting plasma glucose [FPG]) and 2-hour plasma glucose (2hPG) after a 75-g oral glucose challenge with both maternal clinical phenotypes and offspring epigenome at delivery were investigated separately. Results Maternal age, prepregnancy body mass index, and blood pressure measures were associated with both FPG and 2hPG, whereas Chinese ethnicity (P = 1.9 × 10-4), maternal height (P = 1.1 × 10-4), pregnancy weight gain (P = 2.2 × 10-3), prepregnancy alcohol consumption (P = 4.6 × 10-4), and tobacco exposure (P = 1.9 × 10-3) showed significantly opposite associations between the 2 glucose measures. Most importantly, we observed a dichotomy in the effects of these glycemic indices on the offspring epigenome. Offspring born to mothers with elevated 2hPG showed global hypomethylation. CpGs most associated with the 2 measures also reflected differences in gene ontologies and had different associations with offspring birthweight. Conclusions Our findings suggest that 2 traditionally used glycemic indices for diagnosing gestational diabetes may reflect distinctive pathophysiologies in pregnancy, and have differential impacts on the offspring’s DNA methylome.
- Published
- 2021