Hayashi Ikuyo, Yamaguchi Ken, Sumitomo Masahiro, Takakura Kenji, Nagai Narumi, Sakane Naoki
Clinical Research Institute, National Hospital Organization Kyoto Medical Center, 1-1, Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, 612-8551, Japan.
Laboratory of Nutrition Education and Nutritional Physiology, Graduate School of Human Science and Environment, University of Hyogo, Himeji, Japan.
BMC Res Notes. 2020 Apr 3;13(1):199. doi: 10.1186/s13104-020-04961-2.
Low birth weight (LBW) is a major public health issue as it increases the risk of noncommunicable diseases throughout life. However, the genome-wide DNA methylation patterns of full-term LBW infants (FT-LBWs) are still unclear. This exploratory study aimed to analyze the DNA methylation differences in FT-LBWs compared with those in full-term normal birth weight infants (FT-NBWs) whose mothers were nonsmokers and had no complications. Initially, 702 Japanese women with singleton pregnancies were recruited. Of these, four FT-LBWs and five FT-NBWs were selected as references for DNA methylation analysis, and 862,260 CpGs were assessed using Illumina Infinium MethylationEPIC BeadChip. Gene ontology enrichment analysis was performed using DAVID v6.8 software to identify the biological functions of hyper- and hypomethylated DNA in FT-LBWs.
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; "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). EREG was classified into "ovarian cumulus expansion" within the "organism growth and organization" category. Our data imply that LBW might be associated with epigenetic modifications, which regulate the immune system and cell maturation.
低出生体重（LBW）是一个主要的公共卫生问题，因为它会增加个体一生中患非传染性疾病的风险。然而，足月低出生体重婴儿（FT-LBW）的全基因组DNA甲基化模式仍不清楚。这项探索性研究旨在分析FT-LBW与母亲不吸烟且无并发症的足月正常出生体重婴儿（FT-NBW）之间的DNA甲基化差异。最初，招募了702名单胎妊娠的日本女性。其中，选择了4名FT-LBW和5名FT-NBW作为DNA甲基化分析的参考对象，并使用Illumina Infinium MethylationEPIC BeadChip评估了862,260个CpG。使用DAVID v6.8软件进行基因本体富集分析，以确定FT-LBW中高甲基化和低甲基化DNA的生物学功能。
在FT-LBW启动子区域鉴定出483个高差异甲基化基因（DMG）和35个低DMG。高DMG被注释到11个生物学过程中；“巨噬细胞分化”（例如，CASP8）、“凋亡线粒体变化”（例如，BH3）、“核苷酸切除修复”（例如，HUS1）和“炎症反应的负调控”（例如，NLRP12和SHARPIN）。EREG在“生物体生长和组织”类别中被归类为“卵巢卵丘扩张”。我们的数据表明，低出生体重可能与表观遗传修饰有关，表观遗传修饰调节免疫系统和细胞成熟。
