Genome-wide DNA methylation analysis of discordant monozygotic twins reveals consistent sites of differential methylation associated with congenital heart disease

作者全名："Yuan, Xi; Huang, Jiayu; Wen, Li; Novakovic, Boris; Kilby, Mark D.; Tong, Chao; Qi, Hongbo; Saffery, Richard; Baker, Philip N."

作者地址："[Yuan, Xi; Wen, Li; Tong, Chao; Qi, Hongbo; Baker, Philip N.] Chongqing Med Univ, Affiliated Hosp 1, State Key Lab Maternal & Fetal Med Chongqing Munic, Chongqing 400016, Peoples R China; [Huang, Jiayu] Chongqing Med Univ, Affiliated Hosp 1, Reprod Med Ctr, Chongqing 400016, Peoples R China; [Novakovic, Boris; Saffery, Richard] Royal Childrens Hosp, Murdoch Childrens Res Inst, Mol Immun, Melbourne, Vic, Australia; [Novakovic, Boris; Saffery, Richard] Univ Melbourne, Dept Pediat, Parkville, Vic, Australia; [Kilby, Mark D.] Birmingham Womens & Childrens Fdn Trust, Fetal Med Ctr, Birmingham B15 2TG, England; [Kilby, Mark D.] Univ Birmingham, Coll Med & Dent Sci, Inst Metab & Syst Res, Birmingham B15 2TT, England; [Qi, Hongbo] Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet, Chongqing 401147, Peoples R China; [Baker, Philip N.] Univ Leicester, Coll Life Sci, Leicester LE1 7RH, England"

通信作者："Tong, C; Qi, HB; Baker, PN (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, State Key Lab Maternal & Fetal Med Chongqing Munic, Chongqing 400016, Peoples R China.; Saffery, R (通讯作者)，Royal Childrens Hosp, Murdoch Childrens Res Inst, Mol Immun, Melbourne, Vic, Australia.; Baker, PN (通讯作者)，Univ Leicester, Coll Life Sci, Leicester LE1 7RH, England."

来源：GENOMICS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000925000700001

JCR分区：Q2

影响因子：3.4

年份：2023

卷号：115

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：Congenital heart disease; Monozygotic twins; Umbilical cord blood; DNA methylation

摘要："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."

基金机构："National Natural Science Foundation of China [U21A20346, 82171662, 82101711, 82001580, 81520108013]; Chongqing Science and Technology Commission [cstc2021ycjh-bgzxm0192]; Chongqing Health Committee [2019GDRC012]; Chongqing Education Commission [KJZD-K202100404]"

基金资助正文："Sources of funding This work was supported by the National Natural Science Foundation of China (U21A20346, 82171662, 82101711, 82001580, and 81520108013) , Chongqing Science and Technology Commission (cstc2021ycjh-bgzxm0192) , Chongqing Health Committee (2019GDRC012) , and Chongqing Education Commission (KJZD-K202100404) ."