Full-term low birth weight infants have differentially hypermethylated DNA related to immune system and organ growth: A comparison with full-term normal birth weight infant

• DOI: 10.21203/rs.2.21228/v1
• Publication Date: 2020-01-20T16:30:56Z
• Authors: Ikuyo Hayashi; Ken Yamaguchi; Masahiro Sumitomo; Kenji Takakura; Narumi Nagai; Naoki Sakane
• Keywords: Adult; 0301 basic medicine; Science (General); QH301-705.5; Gene; Epigenesis, Genetic; Q1-390; Young Adult; 03 medical and health sciences; Japan; Gene ontology (GO); Term infant; Humans; Biology (General); Promoter Regions, Genetic; 0303 health sciences; DNA methylation; R; Infant, Newborn; DNA Methylation; Infant, Low Birth Weight; Middle Aged; 3. Good health; Research Note; Immune system; Low birth weight; Medicine; Female

Abstract Objective: Low birth weight (LBW) is a major public health issue as it results in a higher risk of non-communicable diseases throughout life. However, the genome-wide DNA methylation patterns of LBW full-term infants (FT-LBWs) are still unclear. The aim of this exploratory study was to compare differences in DNA methylation between FT-LBWs and normal birth weight full-term infants (FT-NBWs) whose mothers were non-smokers and non-complication. Results: A total of 702 Japanese singleton pregnancies were recruited. The prevalence of preterm LBW and FT-LBW was 3.4% and 6.1%, respectively. Four FT-LBWs and five FT-NBWs were selected, genome-wide DNA methylation analysis including 862,260 methylation CpGs was performed. 483 hyper-differentially methylated genes (DMGs) and 35 hypo-DMGs were identified in FT-LBW promoter regions. Hyper-DMGs were annotated to 11 biological processes; intriguingly, “macrophage differentiation” (e.g., CASP8 ), “apoptotic mitochondrial changes” (e.g., BH3 ) , “nucleotide-excision repair” (e.g., HUS1 ) , and “negative regulation of inflammatory response” (e.g., NLRP12 and SHARPIN ) were included within the “immune system” and “DNA metabolism and repair” categories. EREG was classified into “ovarian cumulus expansion” within the “organism growth and organization” category. Our data implies that LBW itself could be associated with epigenetic modulation regarding immune system and cell mature.