Differences of DNA methylation patterns in the placenta of large for gestational age infant.
Differences of DNA methylation patterns in the placenta of large for gestational age infant.
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大于胎龄儿胎盘DNA甲基化模式的差异
DOI：
10.1097/md.0000000000022389
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发表时间：
2020-09-25
期刊：
影响因子：
1.6
通讯作者：
Zou C
中科院分区：
文献类型：
--
作者：
Shen Z;Tang Y;Song Y;Shen W;Zou C
摘要通过分析LGA和适合胎龄（阿加）新生儿胎盘中的脱氧核糖核酸（DNA）甲基化模式，研究大于胎龄（LGA）新生儿后期代谢健康变化的分子机制。LGA组和阿加组各6例。使用Illumina Infinium Human MethylationEPIC BeadChip微阵列分析DNA甲基化，并通过焦磷酸测序和逆转录定量实时聚合酶链反应进行验证。根据LGA和阿加组间差异甲基化区域，通过基因本体论和京都基因百科全书和基因组途径分析构建功能富集分析。临床研究显示LGA新生儿的血红蛋白和血糖明显低于阿加新生儿。出生体重与血红蛋白、血糖呈负相关。全基因组DNA甲基化分析鉴定了17244个甲基化可变位置，实现了全基因组显著性（校正P <0.05）。 34%的甲基化位点位于基因启动子区。碰撞狩猎分析共发现117个差异甲基化区域，映射到107个基因。功能分析显示，13个基因在“粘附和感染过程、内分泌和其他因子调节的钙重吸收、钙信号通路和跨膜转运”中富集。2型糖尿病的病因有哪些在这13个基因中，我们选择了GNAS和钙电压门控通道亚基α 1 G进行焦磷酸测序的独立验证，并通过逆转录-定量实时聚合酶链反应验证了鸟嘌呤核苷酸结合蛋白、钙电压门控通道亚基α 1 G、DECR 1和FK 506结合蛋白11的信使核糖核酸水平。DNA甲基化变异和基因表达差异与LGA新生儿的发生有关，表明宫内环境对后代基因表达的调节作用。此外，通路分析表明，影响胎儿生长的宫内环境可能对涉及胎儿生长、代谢和炎症的多个信号通路具有功能性影响。需要进一步的研究来了解甲基化模式的差异。
Supplemental Digital Content is available in the text Abstract To investigate the molecular mechanisms of later metabolic health changes in large for gestational age (LGA) newborns by analyzing deoxyribonucleic acid (DNA) methylation patterns in the placenta of LGA and appropriate for gestational age (AGA) newborns. A total of 6 placentas of LGA and 6 placentas of AGA newborns were enrolled as LGA group and AGA group. DNA methylation was analyzed using the Illumina Infinium Human MethylationEPIC BeadChip microarrays and verified via pyrosequencing and reverse transcription-quantitative real-time polymerase chain reaction. Functional enrichment analysis were constructed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis based on the differentially methylated regions between LGA and AGA groups. Clinical investigation showed that LGA newborns had significantly lower hemoglobin and blood glucose compared to AGA newborns. Birth weight was negatively correlated to hemoglobin and blood glucose. Genome-wide DNA methylation analysis identified 17 244 methylation variable positions achieving genome-wide significance (adjusted P < .05). 34% methylation variable positions were located in the gene promoter region. A total of 117 differentially methylated regions were revealed by bump hunting analysis, which mapped to 107 genes. Function analysis showed 13 genes enriched in “adhesion and infection process, endocrine and other factor-regulated calcium reabsorption, calcium signaling pathway and transmembrane transport”. Four genes linked to type II diabetes mellitus. Among the 13 genes, we selected GNAS and calcium voltage-gated channel subunit alpha1 G for independent verification of pyrosequencing, and the messenger ribonucleic acid levels of guanine nucleotide binding protein, calcium voltage-gated channel subunit alpha1 G, DECR1, and FK506 binding protein 11 were verified by reverse transcription-quantitative real-time polymerase chain reaction. DNA methylation variation and gene expression differences in placental samples were associated with LGA newborns, which linking the effect of intrauterine environment to regulation of the offspring's gene expression. Furthermore, pathway analysis suggested that intrauterine environment affecting fetal growth might had a functional impact on multiple signaling pathways involved in fetal growth, metabolism, and inflammation. Further studies were required to understand the differences of methylation patterns.
DOI：
10.3109/17477160903111714
发表时间：
2010-04
期刊：
International journal of pediatric obesity : IJPO : an official journal of the International Association for the Study of Obesity
影响因子：
--
作者：
Adkins RM;Krushkal J;Magann EF;Klauser CK;Morrison JC;Ramsey R;Somes G
通讯作者：
Somes G
影响因子：
--
作者：
Murphy R;Mackay D;Mitchell EA
通讯作者：
Mitchell EA