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异常出生体重胎儿父系表达基因1和3的表达与启动子区甲基化及其意义

mRNA expression and promoter methylation of paternally expressed gene 1 and paternally expressed gene 3 in human placenta of abnormal birth weight fetuses

摘要:

目的 研究印记基因父系表达基因1(paternally expressed gene 1,PEG1)与父系表达基因3(paternally expressed gene 3,PEG3)在无妊娠并发症孕妇分娩的异常出生体重儿胎盘组织中的mRNA表达和启动子区甲基化及其意义.方法 应用实时定量PCR技术和基因组DNA亚硫酸氢钠处理后直接测序法检测高出生体重组(出生体重≥4000 g,22例)、低出生体重组(出生体重≤2500 g,14例)和正常出生体重组(出生体重>2500 g且<4000 g,24例)胎盘组织中PEG1与PEG3的mRNA表达和启动子区甲基化,并分析其与出生体重的关系.结果 (1)PEG1与PEG3 mRNA表达水平:高出生体重组分别为11.66±9.01与16.45±10.13,低出生体重组0.84±0.49与0.85±0.67,正常出生体重组1.10±0.77与1.11±0.60.两基因高出生体重组与正常出生体重组比较,差异均有统计学意义(P<0.05),低出生体重组与正常出生体重组比较,差异均无统计学意义(P>0.05);(2)PEG1启动子区甲基化水平:高出生体重组为(49.7±2.3)%,低出生体重组为(50.2±2.1)%,正常出生体重组为(50.3±1.9)%(P>0.05);PEG3启动子区甲基化水平,高出生体重组为(13.1±2.7)%,低出生体重组为(16.7±3.5)%,正常出生体重组为(16.2±1.8)%,仅高出生体重组与正常出生体重组之间差异有统计学意义(P<0.05),但正常出生体重组与低出生体重组之间差异无统计学意义(P>0.05);(3)PEG3 mRNA的表达与启动子区甲基化水平呈负相关(r=-0.963,P<0.01).结论 PEG1和PEG3的表达上调可能是发生高出生体重儿的原因之一,PEG3的启动子区甲基化水平的降低可能参与其表达上调,并且可能与高出生体重的产生相关.

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abstracts:

Objective To study the mRNA expression of two imprinted genes,paternally expressed gene 1(PEG1) and paternally expressed gene 3(PEG3),and their promoter methylation in human placenta of abnormal birth weight(BW)neonates. Methods Placentas were obtained after full term delivery,without any maternal complications during pregnancy,and were divided into 3 groups according to BW:high BW group(n=22,BW≥4000 g),normal BW group(n=14,BW>2500 g and<4000 g)and low BW group(n=24,BW≤2500 g).The mRNA expression of PEG1 and PEG3 were determined by real-time quantitative polymerase chain reaction.Promoter methylation was measured by the bisulfite genomic sequencing method.Results among different groups were compared. Results (1)The mRNA expression of PEGl and PEG3 were 11.66±9.01 and 16.45±10.13 in the high BW group,0.84±0.49 and 0.85±0.67 in the low BW group and 1.10±0.77 and 1.11±0.60 in the normal BW group,respectively.Both genes were significantly up-regulated in the high BW group compared to the normal BW group(P<0.05),but no significant difference was found between the normal and low BW group (P>0.05). (2) The levels of PEG1 promoter methylation were (49. 7± 2. 3) %, (50. 2 ± 2. 1 )% and (50. 3 ± 1.9)% in the high, low and normal BW group (P>0.05), while the levels of PEG3 promoter methylation in the high BW was significantly lower than in the normal BW group [(13.1± 2. 7) % vs (16.2 ±1.8)%, P<0. 05], but no difference was shown between the low BW group (16.7± 3.5)% and the normal BW group (P>0.05). (3)Negative correlation was detected between the expression of PEG:3 and DNA methylation level within the objective fragment of promoter region (r= -0. 963, P<0. 01). Conclusions The up-regulation of PEG1 and PEG3 may be associated with high BW. The reduction of methylation pattern in the promoter region of PEG3 might be involved in the up-regulation of PEG3 and contribute to the mechanism of high BW fetus in turn.

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