印记基因过氧化物酶体增生物激活受体γ共激活因子1α和胰十二指肠同源盒的表达和甲基化与新生儿出生结局的关系

Relationship between mRNA expression and methylation status of imprinted gene PGC-1α and PDX1 and birth outcomes of neonates

目的研究印记基因PGC-1α和PDX1在无妊娠并发症孕妇分娩的异常出生体质量儿胎盘组织中的mRNA表达和甲基化的状态,探讨PGC-1α和PDX1甲基化状态对新生儿出生结局的影响。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质量组、低出生体质量组和正常出生体质量组胎盘组织中PGC-1α和PDX1的mRNA表达和甲基化。结果 PGC-1α、PDX1两基因低出生体质量组与正常出生体质量组比较,差异均有统计学意义(P<0.05),PDX1在高出生体质量组与正常出生体质量组之间差异有统计学意义(P<0.05);PDX1甲基化水平与mRNA的表达呈负相关(r=-0.73,P<0.01)。在低出生体质量组和正常出生体质量组,PGC-1α和PDX1mRNA在胎盘中的表达与出生体质量呈正相关(r值分别为0.87、0.68,P<0.01)。结论 PGC-1α和PDX1的表达下调可能是发生低出生体质量儿的原因之一,甲基化水平的升高可能参与其表达下调,并且可能与低出生体质量儿的产生相关。

Objective To study the mRNA expression of imprinted gene PGC-1α and PDX1,and their methylation status in the human abnormal birth weight placentae without anymaternal complications during pregnancy,and discuss the effect of methylation status of PGC-1α and PDX1 on birth outcomes of 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,normal BW group and low BW group. The mRNA expression of PGC-1α and PDX1 were determined by real-time quantitative polyme polymerase chain reaction. Promoter methylation was measured by the bisulfite genomic sequencing method. Results Both PGC-1αand PDX1 genes were significantly down-regulated in the low BW group compared to the normal BW group,with the difference statistically significant（ P〈 0. 05）,and the difference of PDX1 between the normal and high BW group was statistically significant（ P〈 0. 05）. The methylation level PDX1 was negatively correlated with the expression of PDX1 mRNA（ r =-0. 73,P〈 0. 01）.The expressions of PGC-1α and PDX1 mRNA were positively correlated to the birth weight in the low BW group and normal BW group（ r = 0. 87,r = 0. 68,P〈 0. 01）. Conclusion The down-regulation of PGC-1α and PDX1 may be associated with low BW. The increment of methylation pattern of PGC-1α and PDX1 might be involved in the down-regulation of PGC-1α and PDX1 and contribute to the mechanism of low BW fetus in turn.