对不一致的同卵双胞胎进行全基因组DNA甲基化分析，揭示了与先天性心脏病相关的差异甲基化的一致位点。
Genome-wide DNA methylation analysis of discordant monozygotic twins reveals consistent sites of differential methylation associated with congenital heart disease.
作者信息
Yuan Xi, Huang Jiayu, Wen Li, Novakovic Boris, Kilby Mark D, Tong Chao, Qi Hongbo, Saffery Richard, Baker Philip N
机构信息
State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Reproductive Medicine Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
出版信息
Genomics. 2023 Mar;115(2):110565. doi: 10.1016/j.ygeno.2023.110565. Epub 2023 Jan 20.
BACKGROUND
Despite being essentially genetically identical, monozygotic (MZ) twins can be discordant for congenital heart disease (CHD), thus highlighting the importance of in utero environmental factors for CHD pathogenesis. This study aimed to identify the epigenetic variations between discordant MZ twin pairs that are associated with CHD at birth.
METHODS
Cord blood of CHD-discordant MZ twins from the Chongqing Longitudinal Twin Study Cohort was subjected to whole-genome bisulfite sequencing, then validated by MeDIP-qPCR and qRT-PCR.
RESULTS
379 DMRs mapped to 175 differentially methylated genes (DMGs) were associated with CHD. Functional enrichment analysis identified these DMGs are involved in histone methylation, actin cytoskeleton organization, the regulation of cell differentiation, and adrenergic signaling in cardiomyocytes. Of note, SPESP1 and NOX5 were hypermethylated in CHD, and associated with lower gene expression levels.
CONCLUSIONS
Specific DNA methy (DNAm) variations in cord blood were associated with CHD, thus illustrating new biomarkers and potential interventional targets for CHD.
TRIAL REGISTRATION
ChiCTR-OOC-16008203, registered on 1 April 2016 at the Chinese Clinical Trial Registry.
背景
尽管单卵（MZ）双胞胎在基因上基本相同，但他们在先天性心脏病（CHD）方面可能存在不一致，这凸显了子宫内环境因素在CHD发病机制中的重要性。本研究旨在确定出生时与CHD相关的不一致MZ双胞胎对之间的表观遗传变异。
方法
对来自重庆双胞胎纵向研究队列的CHD不一致MZ双胞胎的脐带血进行全基因组亚硫酸氢盐测序，然后通过甲基化DNA免疫沉淀定量PCR（MeDIP-qPCR）和定量逆转录聚合酶链反应（qRT-PCR）进行验证。
结果
379个差异甲基化区域（DMR）映射到175个差异甲基化基因（DMG）与CHD相关。功能富集分析表明，这些DMG参与组蛋白甲基化、肌动蛋白细胞骨架组织、细胞分化调控以及心肌细胞中的肾上腺素能信号传导。值得注意的是，SPESP1和NOX5在CHD中甲基化程度较高，且与较低的基因表达水平相关。
结论
脐带血中特定的DNA甲基化（DNAm）变异与CHD相关，从而阐明了CHD的新生物标志物和潜在的干预靶点。
试验注册
在中国临床试验注册中心于2016年4月1日注册，注册号为ChiCTR-OOC-16008203。
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