Hu Wensheng, Weng Xiaoling, Dong Minyue, Liu Yun, Li Wenjuan, Huang Hefeng
Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou, Zhejiang Province, 310006, China.
Institutes of Biomedical Sciences, Fudan University, 220 Handan Road, Shanghai, China.
BMC Genet. 2014 Sep 9;15:96. doi: 10.1186/s12863-014-0096-5.
Preeclampsia reduces placental expression and activity of 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2), leading to an increase in fetal glucocordicoids. The latter has been proposed to be associated with low birth weight and high risk of metabolic diseases in later life of the offspring. This investigation aims to delineate the alteration in methylation levels at CpG sites of HSD11B2 promoter.
Methylation levels of HSD9-2, HSD9-3, HSD23-2 and HSD23-3 and the mean methylation level were significantly lower in preeclampsia than in normal pregnancy (P = 0.002, 0.031, 0.047 and 0.001, respectively and P < 0.001 in mean). The mean methylation level was significantly correlated with preeclampsia after the adjustment of birth weight, maternal age, gestational age at delivery and fetal gender (r = 0.325, P < 0.001).
Preeclampsia reduced methylation level at fetal HSD11B2 promoter. A positive correlation existed between HSD11B2 promoter methylation and preeclampsia. Our findings suggest that the methyaltion status of HSD11B2 promoter is a potentially accessible biomarker for preeclampsia. However, further studies are required to address the mechanisms of thehypomethylation at HSD11B2 promoter and the significance of the hypomethylation in the development of metabolic diseases of the fetals born to preeclamptic women.
子痫前期会降低胎盘2型11β-羟基类固醇脱氢酶(HSD11B2)的表达和活性,导致胎儿糖皮质激素增加。后者被认为与低出生体重以及后代成年后患代谢性疾病的高风险有关。本研究旨在描绘HSD11B2启动子CpG位点甲基化水平的变化。
子痫前期患者中HSD9-2、HSD9-3、HSD23-2和HSD23-3的甲基化水平以及平均甲基化水平显著低于正常妊娠(P分别为0.002、0.031、0.047和0.001,平均甲基化水平P<0.001)。在调整出生体重、母亲年龄、分娩时的孕周和胎儿性别后,平均甲基化水平与子痫前期显著相关(r=0.325,P<0.001)。
子痫前期降低了胎儿HSD11B2启动子的甲基化水平。HSD11B2启动子甲基化与子痫前期之间存在正相关。我们的研究结果表明,HSD11B2启动子的甲基化状态是子痫前期一个潜在的可获取生物标志物。然而,需要进一步研究来探讨HSD11B2启动子低甲基化的机制以及该低甲基化在子痫前期孕妇所生胎儿代谢性疾病发生中的意义。