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Intrauterine growth restriction (IUGR), a serious complication of perinatal period, results in short-term and long-term health problems, particular in metabolic and brain disorders.However, the exact cause of IUGR remains unclear.Recently, some evidences indicated that epigenetic modification plays an important role in IUGR-induced adult disease.Hence, in this study the methylation status and gene expression profiles of infants with IUGR were compared with normal controls to investigate the changes in epigenetic regulation and gene expression induced by IUGR.DNA samples extracted from blood samples of infants with IUGR and normal controls appropriate for gestational age (AGA) were analyzed with Illumina Human Methylation 450k array to identify differences in genome-wide DNA methylation, and DNA methylation changes of CpGs were verified by Mass ARRAY.Moreover, an IUGR rat model was established by maternal malnutrition method, and gene expression profiles associated with progressive DNA methylation changes in brain tissue were detected using microarray Affymetrix Rat Gene 2.0ST.Based on DNA methylation array, 5460 CpG loci targeting 2265 genes are differentially methylated between IUGR and AGA.1311 differentially expressed genes were obtained by Microarray.After comparing DNA methylation data with gene expression data, 49 genes showed a negative correlation between DNA methylation and gene expression.For KEGG pathway enrichment for gene presenting differential pattern in either mRNA expression or DNA methylation, 27 commonly enriched pathways were identified, which involved sugar, fat and protein metabolism, diseases of the nervous system, cancer, and immunomodulation and endocrine regulation, indicating that d methylation abnormalities induced by IUGR, were closely related with brain development and metabolism.These findings suggest the epigenetic regulatory mechanisms on corresponding gene expression which may play a role in the adult-onset diseases induced by IUGR, providing a chance to develop novel epigenetic-based therapeutic strategy for IUGR.