胎盘CYP11A1基因启动子甲基化与胎儿生长受限和子痫前期的相关性
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摘要
目的探讨CYP11A1基因启动子甲基化改变与胎儿生长受限(FGR)和或子痫前期(PE)的相关性。方法针对正常妊娠对照26例、胎儿生长受限(FGR) 40例、子痫前期(PE) 40例及胎儿生长受限合并子痫前期(FGR-PE) 18例标本,采用焦磷酸测序和实时荧光定量PCR,检测CYP11A1基因的甲基化和mRNA表达水平。结果胎盘中CYP11A1基因在FGR、FGR-PE、PE中呈低甲基化水平,尤其在FGR-PE中CYP11A1基因甲基化水平相对更低;同时,可能受到CYP11A1基因低甲基化状态的反向调控,CYP11A1基因的mRNA表达水平显著上调。结论CYP11A1基因甲基化作为胎盘组织特异性表观遗传学分子标志物,与胎儿生长受限、子痫前期等疾病相关。
Objective To investigate the correlation between CYP11A1 gene promter methylation and fetal growth restriction( FGR) and preeclampsia( PE).Methods The bisulfite pyrosequncing assay and qRT-PCR were used to demonstrate CYP11A1 methylation and expression patterns respectively in FGR,PE and FGR-PE,as well as Control associated placentas and cord blood of fetus. Results The promoter of CYP11A1 was found to be significantly hypomethylated in FGR,PE and FGR-PE placentas. And the methylation of CYP11A1 gene was relatively lower in FGR-PE than other case. Meanwhile the increased CYP11A1 expression was inversely modulate with CYP11A1 hypomethylation FGR,PE and FGR-PE placentas. which only found in placenta but not in cord blood of fetus.Conclusions As a tissue-specific epigenetic marker,CYP11A1 gene is associated with fetal growth restriction and preeclampsia or both.
Objective To investigate the correlation between CYP11A1 gene promter methylation and fetal growth restriction( FGR) and preeclampsia( PE).Methods The bisulfite pyrosequncing assay and qRT-PCR were used to demonstrate CYP11A1 methylation and expression patterns respectively in FGR,PE and FGR-PE,as well as Control associated placentas and cord blood of fetus. Results The promoter of CYP11A1 was found to be significantly hypomethylated in FGR,PE and FGR-PE placentas. And the methylation of CYP11A1 gene was relatively lower in FGR-PE than other case. Meanwhile the increased CYP11A1 expression was inversely modulate with CYP11A1 hypomethylation FGR,PE and FGR-PE placentas. which only found in placenta but not in cord blood of fetus.Conclusions As a tissue-specific epigenetic marker,CYP11A1 gene is associated with fetal growth restriction and preeclampsia or both.
引文
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[4]张庆华,郝胜菊,孙小红,等.胎儿生长受限的DNA甲基化研究进展[J].国际生殖健康/计划生育杂志,2016,35:137-141.
[5] Ferreira JCPB. Epigenetic regulation in the placenta and its role in fetal growth[J]. Doctoral,2012,1-340.
[6] Iglesiasplatas I, Court F, Monk D. Distinct promoter methylation and isoform-specific expression of RASFF1A in placental biopsies from complicated pregnancies.[J].Placenta,2015,36:397-402.
[7] Zhao Y, Gong X, Chen L, et al. Site-specific methylation of placental HSD11B2 gene promoter is related to intrauterine growth restriction[J]. Eur J Hum Genet,2014,22:734-740.
[8] Ben-Zimra M,Koler M,Orly J. Transcription of cholesterol side-chain cleavage cytochrome P450 in the placenta:activating protein-2 assumes the role of steroidogenic factor-1 by binding to an overlapping promoter element[J]. Mol endocrinol,2002,16:1864-1880.
[9] Hogg K,Blair JD,Mcfadden DE,et al. Early onset preeclampsia is associated with altered DNA methylation of cortisol-signalling and steroidogenic genes in the placenta.[J]. PLoS One,2013,8:e62969. doi:10.1371/journal.pone.0062969.
[10]何国琳,刘兴会.子痫前期患者胎盘CYP11A基因高表达与滋养细胞异常凋亡的研究[C].中华医学会第十次全国妇产科学术会议. 2012.
[11] Adkins RM,Tylavsky FA,Krushkal J. Newborn umbilical cord blood DNA methylation and gene expression levels exhibit limited association with birth weight[J]. Chem Biodivers,2012,9:888-899.
[2] Williams D. Long-term complications of preeclampsia[J]. Semin Nephrol,2011,31:111-122.
[3] Roberts DJ,Post MD. The placenta in pre-eclampsia and intrauterine growth restriction[J]. J Clin Pathol,2008,61:1254-1260.
[4]张庆华,郝胜菊,孙小红,等.胎儿生长受限的DNA甲基化研究进展[J].国际生殖健康/计划生育杂志,2016,35:137-141.
[5] Ferreira JCPB. Epigenetic regulation in the placenta and its role in fetal growth[J]. Doctoral,2012,1-340.
[6] Iglesiasplatas I, Court F, Monk D. Distinct promoter methylation and isoform-specific expression of RASFF1A in placental biopsies from complicated pregnancies.[J].Placenta,2015,36:397-402.
[7] Zhao Y, Gong X, Chen L, et al. Site-specific methylation of placental HSD11B2 gene promoter is related to intrauterine growth restriction[J]. Eur J Hum Genet,2014,22:734-740.
[8] Ben-Zimra M,Koler M,Orly J. Transcription of cholesterol side-chain cleavage cytochrome P450 in the placenta:activating protein-2 assumes the role of steroidogenic factor-1 by binding to an overlapping promoter element[J]. Mol endocrinol,2002,16:1864-1880.
[9] Hogg K,Blair JD,Mcfadden DE,et al. Early onset preeclampsia is associated with altered DNA methylation of cortisol-signalling and steroidogenic genes in the placenta.[J]. PLoS One,2013,8:e62969. doi:10.1371/journal.pone.0062969.
[10]何国琳,刘兴会.子痫前期患者胎盘CYP11A基因高表达与滋养细胞异常凋亡的研究[C].中华医学会第十次全国妇产科学术会议. 2012.
[11] Adkins RM,Tylavsky FA,Krushkal J. Newborn umbilical cord blood DNA methylation and gene expression levels exhibit limited association with birth weight[J]. Chem Biodivers,2012,9:888-899.
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