Altered DNA methylation in neonates born large-for-gestational-age is associated with cardiometabolic risk in children

作者:Lin, Xian-hua; Wu, Dan-dan; Gao, Ling; Zhang, Jun-yu; Pan, Hai-tao; Wang, Hui; Li, Cheng; Zhang, Ping; Guo, Meng-xi; Wu, Yan-ting; Tan, Ya-jing; Jin, Li; Xiang, Yu-qian; Li, Ju-xue; Sheng, Jian-zhong; Huang, He-feng*
来源:Oncotarget, 2016, 7(52): 86511-86521.
DOI:10.18632/oncotarget.13442

摘要

Background: Infants being born Large-for-gestational-age (LGA) are prone to developing cardiometabolic disease. However, the underlying mechanisms remain unclear. @@@ Results: Clinical investigation showed that children born LGA had significantly higher serum level of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and insulin, ratio of TC/high-density lipoprotein-cholesterol (HDL-c) compared to children born appropriate for gestational age (AGA). Birth weight (BW) was positively correlated to TC, LDL-c, and the ratio of TC/HDL in serum. Genome-wide DNA methylation analyzed in umbilical cord blood of controls and macrosomia cases. We identified 3459 methylation variable positions (MVPs) achieving genome- wide significance (adjusted P-value < 0.05) with methylation differences of >= 5%. A total of 327 MVPs were filtered by methylation differences of >= 7% located within an island, which mapped to 213 genes. Function analysis using Ingenuity Pathway Analysis showed 16 genes enriched in "cardiovascular disease". Four genes included contributed to hyperlipidemia. @@@ Materials And Methods: Fifty-eight children aged 3-6 years born LGA and 123 subjects born AGA were enrolled. Anthropometric parameters and blood pressure (BP) were measured, and metabolic assessment was performed in all subjects. Genome-wide DNA methylation in umbilical blood was assayed by the 450K BeadChip in six AGA and six macrosomia newborns. @@@ Conclusions: Our data indicate that excess birth weight may increase the risk of lipid dysfunction in children aged 3-6 years. It might through reprogramming a group of genes correlated to cardiovascular disease. The genes identified in this study might be potential biomarker for cardiometabolic disease.